Abstract
The brain stem is composed of the midbrain (the mesencephalon) and the hindbrain (the rhombencephalon), and is, at least during development, segmentally organized. The midbrain is composed of two temporarily present segments known as mesomeres, whereas the hindbrain is composed of eight, and more recently of 12, rhombomeres (r0–r12), counting the isthmic rhombomere as r0. The cerebellum arises from the first and second rhombomere (r0 and r1). The brain stem also contributes 10 of the 12 cranial nerves, III–XII. A great number of genes are involved in the proper development of the brain stem. The isthmus organizer regulates the early development of the mesencephalon and of the rostral part of the rhombencephalon. Each rhombomere is characterized by a unique combination of Hox genes, its Hox code. In mice, spontaneous and targeted (knockout) mutations in these genes result in specific, rhombomere-restricted disruptions in the development of motor nuclei of cranial nerves. Such a “rhombomeropathy” has been described for the HOXA1 gene.
In this chapter, patterning of the brain stem and its segmentation are discussed in ► Sect. 7.2, followed by an overview of the development and developmental disorders of the cranial nerves (► Sect. 7.3). In ► Sect. 7.4, the development of the auditory system, its molecular basis, some of its disorders, and genes associated with deafness are discussed. Clinical cases illustrate some major malformations.
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References
Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C et al (1997) A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet 15:157–164
Acampora D, Gulisano M, Broccoli V, Simeone A (2001) Otx genes in brain morphogenesis. Prog Neurobiol 64:69–95
Aicardi J (1998) Diseases of the nervous system in childhood, 2nd edn. Mac Keith, London
Alasti F, Sadeghi A, Sanati MH, Farhadi M, Stollar E, Somers T, Van Camp G (2008) A mutation in HOXA2 is responsible for autosomal-recessive microtia in an Iranian family. Am J Hum Genet 82:982–991
Alaynick WA, Jessell TM, Pfaff SL (2011) SnapShot: spinal cord development. Cell 146:178–178
Al-Barradie R, Yamada K, St. Hilaire C, Chan WM, Andrews C, McIntosh N et al (2002) Duane radial ray syndrome (Okihori syndrome) maps to 20q13 and results from mutations in SAL1A, a new member of the SAL family. Am J Hum Genet 71:1195–1199
Alexandre P, Wassef M (2003) The isthmic organizer links anteroposterior and dorsoventral patterning in the mid/hindbrain by generating roof plate structures. Development 130:5331–5338
Alford LR, Arnos KS, Fox M, Lin JW, Palmer CG, Pandya A et al (2014) American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiological diagnosis of hearing loss. Genet Med 16:347–355
Alheid GF, McCrimmon DR (2008) The chemical neuroanatomy of breathing. Resp Physiol Neurobiol 164:3–11
Allanson J (2004) Genetic hearing loss associated with external ear anomalies. In: Toriello HV, Reardon W, Gorlin RJ (eds) Hereditary hearing loss and its syndromes, 2nd edn. Oxford University Press, Oxford, pp 83–125
Altman J, Bayer SA (1982) Development of the cranial nerve ganglia and related nuclei in the rat. Adv Anat Embryol Cell Biol 74:1–90
Altmann F (1951) Malformations of the auricle and the external auditory meatus. Arch Otolaryngol 54:115–139
Altmann F (1955) Congenital atresia of the ear in man and animals. Ann Otol Rhinol Laryngol 64:824–858
Amiel J, Laudier B, Attie-Bitach T, Trang H, de Pontual L, Gener B et al (2003) Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital hypoventilation syndrome. Nat Genet 33:459–461
Angelini C, Trimouille A, Arveiler B, Espil-Taris C, Ichinose N, Lasseaux E et al (2021) CHN1 and Duane retraction syndrome: expanding the phenotype to cranial nerves development disease. Eur J Med Genet 64:104188
Anson BJ, Davies J (1980) Embryology of the ear: developmental anatomy of the ear. In: Paparella MM, Shumrick DA, Meyerhoff WL, Seid AB (eds) Otolaryngology, 2nd edn. Saunders, Philadelphia, PA, pp 3–25
Anson BJ, Bast TH, Cauldwell EW (1948) The development of the auditory ossicles, the otic capsule and the extracapsular tissues. Ann Otol Rhinol Laryngol 57:603–632
Anson BJ, Hanson JS, Richany SF (1960) Early embryology of the auditory ossicles and associated structures in relation to certain anomalies observed clinically. Ann Otol Rhinol Laryngol 69:427–447
Anthwal N, Thompson H (2016) The development of the mammalian outer and middle ear. J Anat (Lond) 228:217–232
Arnold JS, Braunstein EM, Ohyama T, Groves AK, Adams JC, Braun C, Morrow BE (2006) Tissue-specific roles of Tbx1 in the development of the outer, middle and inner ear, defective in 22q11D5 patients. Hum Mol Genet 15:1629–1639
Ashwell KW, Watson CR (1983) The development of facial motoneurones in the mouse—neuronal death and the innervation of the facial muscles. J Embryol Exp Morphol 77:117–141
Auclair F, Valdes N, Marchand R (1996) Rhombomere-specific origin of the branchial and visceral motoneurons of the facial nerve in the rat embryo. J Comp Neurol 369:451–461
Baker CV, Bronner-Fraser M (2001) Vertebrate cranial placodes. I. Embryonic induction. Dev Biol 232:1–61
Barkovich AJ, Millen KJ, Dobyns WB (2007) A developmental classification of malformations of the brainstem. Ann Neurol 62:625–639
Barkovich AJ, Millen KJ, Dobyns WB (2009) A developmental and genetic classification for midbrain-hindbrain malformations. Brain 132:3199–3230
Barrow JR, Stadler HS, Capecchi MR (2000) Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development 127:933–944
Barth PG, Majoie CB, Caan MWA, Weterman MAJ, Kyllerman M, Smit LME et al (2007) Pontine tegmental cap dysplasia: a novel brain malformation with a defect in axonal guidance. Brain 130:2258–2266
Barth PG, de Vries LS, Nikkels PGJ, Troost D (2008) Congenital brainstem disconnection associated with a syrinx of the brainstem. Neuropediatrics 39:1–7
Barth PG, Aronica E, Fox S, Fluiter K, Weterman MAJ, Poretti A et al (2017) Deregulated expression of EZH2 in congenital brainstem disconnection. Neuropathol Appl Neurobiol 43:358–365
Baxter A (1971) Dehiscence of the Fallopian canal. J Laryngol Otol 85:587–594
Bayer SA, Altman J, Russo RJ, Zhang X (1995) Embryology. In: Duckett S (ed) Pediatric neuropathology. Williams & Wilkins, Baltimore, MD, pp 54–107
Beck C (1970) Duplication of the external auditory ear. HNO 18:307–308
Bermingham NA, Vollrath MA, Eatock RA, Hassan BA, Price SD, Ben-Arie N et al (1999) Math1: an essential gene for the generation of inner ear hair cells of the mouse inner ear. Science 284:1837–1841
Birnholtz JC, Benacerraf BR (1983) The development of fetal hearing. Science 222:516–518
Bitner-Glindzicz M (2002) Hereditary deafness and phenotyping in humans. Br Med Bull 63:73–94
Blackburn J, Chapur VF, Stephens JA, Zhao J, Shepher A, Pierson CR, Otero JJ (2020) Revisiting the neuropathology of sudden infant death syndrome (SIDS). Front Neurol 11:594550
Blessing WW, Benarroch EE (2012) Lower brain stem regulation of visceral, cardiovascular, and respiratory function. In: Mai JK, Paxinos G (eds) The human nervous system, 3rd edn. Elsevier, Amsterdam, pp 1058–1073
Bok J, Chang W, Wu DK (2007) Patterning and morphogenesis of the vertebrate inner ear. Int J Dev Biol 51:521–533
Bonnet C, El-Amraoui A (2012) Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches. Curr Opin Neurol 25:42–49
Bordley JE (1973) The effect of viral infection on hearing. A state-of-the-art report with special emphasis on congenital rubella. Arch Otolaryngol 98:217
Bosley TM, Salih MA, Alorainy IA, Oystreck DT, Nester M, Abu-Amero KK et al (2007) Clinical characterization of the HOXA1 syndrome BSAS variant. Neurology 69:1245–1253
Bosley TM, Alorainy IA, Salih MA, Aldhalaan HM, Abu-Amero KK, Oystreck DT et al (2008) The clinical spectrum of homozygous HOXA1 mutations. Am J Med Genet Part A 146A:1235–1240
Bouchard M, de Caprona D, Busslinger M, Xu P, Fritzsch B (2010) Pax2 and Pax8 cooperate in mouse inner ear morphogenesis and innervation. BMC Dev Biol 10:89
Bouwes Bavinck JN, Weaver DD (1986) Subclavian artery supply disruption sequence: hypothesis of a vascular etiology of Poland, Klippel-Feil, and Möbius anomalies. Am J Med Genet 23:903–918
Bredberg G (1968) Cellular pattern and nerve supply of the organ of Corti. Acta Otolaryngol Suppl 236:1–135
Briscoe J, Sussel L, Serup P, Hartigan-O’Connor D, Jessell TM, Rubenstein JLR, Ericson J (1999) Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 398:622–627
Brooker R, Hozumi K, Lewis J (2006) Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear. Development 133:1277–1286
Brookhouser PE, Bordley JE (1973) Congenital rubella deafness. Pathology and pathogenesis. Arch Otolaryngol 98:252–257
Brown SDM, Hardisty-Hughes RE, Mbura P (2008) Quiet as a mouse: dissecting the molecular and genetic basis of hearing. Nat Rev Genet 9:277–290
Brown KK, Viana LM, Helwig CC, Artunduaga MA, Quintanilla-Dieck L, Jarrin P et al (2013) HOXA2 haploinsufficiency in dominant bilateral microtia and hearing loss. Hum Mutat 34:1347–1351
Brunet J-F, Pattyn A (2002) Phox2 genes—from patterning to connectivity. Curr Opin Genet Dev 12:435–440
Bryant TH, Yoshida S, de Castro D, Lipski J (1993) Expiratory neurons of the Bötzinger complex in the rat: a morphological study following intracellular labeling with biocytin. J Comp Neurol 335:267–282
Burton Q, Cole KC, Mulheisen M, Chang W, Wu DK (2004) The role of Pax2 in mouse inner ear development. Dev Biol 272:161–175
Bush WD, Simon JD (2007) Quantification of Ca2+ binding to melanin supports the hypothesis that melanosomes serve a functional role in regulating calcium homeostasis. Pigment Cel Res 20:134–139
Büttner-Ennever JA, Akert K (1981) Medial rectus subgroups of the oculomotor nucleus and their abducens internuclear input in monkey. J Comp Neurol 197:17–27
Büttner-Ennever JA, Horn AKE (2004) Reticular formation: eye movements, gaze and blink. In: Paxinos G, Mai JK (eds) The human nervous system, 2nd edn. Elsevier, Amsterdam, pp 479–510
Calabrese G, Stuppia L, Morizio E, Guanciali Franchi P, Pompetti F, Mingarelli T et al (1998) Detection of an insertion deletion of region 8q13-q21.2 in a patient with Duane syndrome: implications for mapping and cloning a Duane gene. Eur J Hum Genet 6:187–193
Calabrese G, Telvi L, Capodiferro F, Morizio E, Pizzuti A, Stuppi R et al (2000) Narrowing the Duane syndrome critical region at chromosome 8q13 down to 40 kb. Eur J Hum Genet 8:319–324
Canning CA, Lee L, Irving C, Mason I, Jones CM (2007) Sustained interactive Wnt and FGF signaling is required to maintain isthmic identity. Dev Biol 305:276–286
Carpenter EM, Goddard JM, Chisaka O, Manley NR, Capecchi MR (1993) Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain. Development 118:1063–1075
Ceruti S, Stinckens C, Cremers C, Casselman JW (2002) Temporal bone anomalies in the branchio-oto-renal syndrome: detailed computer tomographic and magnetic resonance imaging findings. Otol Neurotol 23:200–207
Chan DK, Chang KW (2014) GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype and auditory phenotype. Laryngoscope 124:E34–E53
Chang W, Nunes FD, De Jesus-Escobar JM, Harland RM, Wu DK (1999) Ectopic noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear. Dev Biol 216:369–381
Chang EH, Menezes M, Meyer NC, Cucci RA, Vervoort VS, Schwartz CE, Smith RJ (2004) Branchio-oto-renal syndrome: the mutation spectrum of EYA1 and its phenotypic consequences. Hum Mut 23:582–589
Chellapa R, Li S, Pauley S, Jahan I, Jin K, Xiang M (2008) Barhl1 regulatory sequences required for cell-specific gene expression and autoregulation in the inner ear and central nervous system. Mol Cell Biol 28:1905–1914
Chen J, Nathans J (2007) Estrogen-related receptor beta/NR3B2 controls epithelial cell fate and endolymph production by the stria vascularis. Dev Cell 13:325–337
Chen P, Johnson JE, Zoghbi HY, Segil N (2002) The role of Math1 in inner ear development: uncoupling the establishment of the sensory primordium from hair cell fate determination. Development 129:2495–2505
Chen W, Kahrizi K, Meyer NC, Riazalhosseini Y, Van Camp G, Najmabadi H, Smith RJ (2005) Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus. J Med Genet 42:e61
Cheng L, Desai J, Miranda CJ, Duncan JS, Qiu W, Nugent AA et al (2014) Human CFEOM1 mutations attenuate KIF21A autoinhibition and cause oculomotor axon stalling. Neuron 82:334–339
Chi CL, Martinez S, Wurst W, Martin GR (2003) The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development 130:2633–2644
Chilton JK, Gurthrie S (2017) Axons get ahead: insights into axon guidance and congenital cranial dysinnervation disorders. Dev Neurobiol 77:861–875
Chizhikov VV, Iskusnykh IY, Fattakhov N, Fritzsch B (2021) Lmx1a and Lmx1b are redundantly required for the development of multiple components of the mammalian auditory system. Neuroscience 452:247–264
Cioffi JA, Yue WY, Mendolia-Loffredo S, Hansen KR, Wackym PA, Hansen MR (2010) MicroRNA-21 overexpression contributes to vestibular schwannoma cell proliferation and survival. Otol Neurotol 31:1455–1462
Collin RW, Kalay E, Tariq M, Peters T, van der Zwaag B, Venselaar H et al (2008a) Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment. Am J Hum Genet 82:125–138
Collin RW, Chellapa R, Pauw RJ, Vriend G, Oostrik J, van Drunen W et al (2008b) Missense mutations in POU4F3 cause autosomal dominant hearing impairment DFNA15 and affect subcellular localization and DNA binding. Hum Mutat 29:545–554
Cordes SP (2001) Molecular genetics of cranial nerve development in mouse. Nat Rev Neurosci 2:611–623
Corwin JT, Warchol ME (1991) Auditory hair cells: structure, function, development, and regeneration. Annu Rev Neurosci 14:301–333
Counter SA (2002) Fetal and neonatal development of the auditory system. In: Lagercrantz H, Hanson M, Evrard P, Rodeck C (eds) The newborn brain. Neuroscience and clinical applications. Cambridge University Press, Cambridge, pp 226–251
Coyle B, Coffey R, Armour JA, Gausden E, Hochberg Z, Grossman A et al (1996) Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4. Nat Genet 12:421–423
Cremers CWRJ, Delleman WJW (1988) Usher’s syndrome, temporal lobe pathology. Int J Pediatr Otolaryngol 16:23–30
Cremers CWRJ, Teunissen E (1991) A classification of minor congenital ear anomalies and short- and long-term results of surgery in 104 ears. In: Charachon R, Garcia-Ibanes E (eds) Long-term results and indications in otology and otoneurosurgery. Kugler, Amsterdam, pp 11–12
Cremers CWRJ, Teunissen E, Marres EH (1988) Classification of congenital aural atresia and results of constructive surgery. Adv Otorhinolaryngol 40:9–14
Cruysberg JRM, Huygen PLM (1990) Congenital monocular adduction palsy with synergistic divergence diagnosed in a young infant. Neuro-ophthalmol 10:253–256
Cruysberg JRM, Mtanda AT, Duinkerke-Eerola KU, Stoelinga GBA (1986) Bilateral Duane’s retraction syndrome associated with congenital panhypopituitarism. Neuro-ophthalmol 6:165–168
Cruysberg JRM, Mtanda AT, Duinkerke-Eerola KU, Huygen PLM (1989) Congenital adduction palsy and synergistic divergence; a clinical and electro-oculographic study. Br J Ophthalmol 73:68–75
Cruysberg JRM, Draaijer RW, Pinckers A, Brunner HG (1998) Congenital corneal anesthesia in children with the VACTERL association. Am J Ophthalmol 125:96–98
Dallos P (2008) Cochlear amplification, outer hair cells and presrin. Curr Opin Neurobiol 18:370–376
Danielian PS, Muccino D, Rowitch DH, Michael SK, McMahon AP (1998) Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol 8:1323–13S2
Daugier S, Pattyn A, Lafaso F, Gaultier C, Goridis C, Gallego J, Brunet JF (2003) Phox2b controls the development of peripheral chemoreceptors and afferent visceral pathways. Development 130:6635–6642
de Kok YG, van der Marel SM, Bitner-Glindzicz M, Huber I, Monaco AP, Malcolm S et al (1995) Association between X-linked deafness and mutations in the POU domain gene POU3F4. Science 267:685–688
De Leenheer EM, Bosman AJ, Kunst HP, Huygen PL, Cremers CW (2004) Audiological characteristics of some affected members of a Dutch DFNA13/COL11A2 family. Ann Otol Rhinol Laryngol 113:922–929
de Sa DJ (1997) The ear. In: Gilbert-Barness E (ed) Potter’s pathology of the fetus and infant. Mosby, St. Louis, MI, pp 1522–1540
De Siati RD, Rosenzweig F, Gersdorff G, Gregoire A, Rombaux P, Deggouj N (2020) Auditory neuropathy spectrum disorders: from diagnosis to treatment, literature review and case report. J Clin Med 9:1074
del Castillo FJ, del Castillo I (2011) The DFNB1 subtype of autosomal recessive non-syndromic hearing impaitment. Front Biosci 16:3252–3274
Delás MJ, Briscoe J (2020) Repressive interactions in gene regulatory networks: when you have no other choice. Curr Top Dev Biol 139:239–266
Dennis DJ, Han S, Schuurmans C (2019) bHLH transcription factors in neural development, disease, and reprogramming. Brain Res 1705:48–65
Deol MS (1964) The abnormalities of the inner ear in Kreisler mice. J Embryol Exp Morphol 12:475–490
Di Bonito M, Studer M (2017) Cellular and molecular underpinnings of neuronal assembly in the central auditory system during mouse development. Front Neur Circuits 11:18
Di Donato N, Kuchler A, Vergano S, Heinritz W, Bodurtha J, Merchant SR et al (2016) Update on the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome. Am J Med Genet A 170A:2644–2651
Diáz C, Glover JC (2022) The vestibular column in the mouse: a rhombomeric perspective. Front Neuroanat 15:806815
Dietzel K (1961) Über die Dehiszenzen des Facialiskanals. Z Laryngol Rhinol Otol 40:366–376
Doherty E, Macy M, Wang S, Dykeman C, Melanson M, Engle E (1999) CFEOM3: a new extraocular congenital fibrosis syndrome that maps to 16q24.2-q24.3. Invest Ophthalmol Vis Sci 40:1687–1694
Dror AA, Avraham KB (2009) Hearing loss: mechanisms revealed by genetics and cell biology. Annu Rev Genet 43:411–457
Dror AA, Avraham KB (2010) Hearing impairment: a panoply of genes and function. Neuron 68:293–308
Druckenbrod NR, Goodrich LV (2015) Sequential retraction segregates SGN processes during target selection in the cochlea. J Neurosci 35:26221–16235
Drummond MC, Belyantseva IA, Friderici KH, Friedman TB (2012) Actin in hair cells and hearing loss. Hear Res 288:89–99
Duane A (1905) Congenital deficiency of abduction associated with impairment of abduction, retraction movements, contractions of the palpebral fissure and oblique movements of the eye. Arch Ophthalmol 34:133–159
Dubreuil V, Ramanatsoa N, Trochet D, Vauborg V, Amiel J, Gallego J et al (2008) A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apneu, and specific loss of parafacial neurons. Proc Natl Acad Sci U S A 105:1067–1072
Dvorakova M, Macova I, Bohuslavova R, Anderova M, Fritzsch B, Pavlinkova G (2020) Early ear neuronal development, but not olfactory or lens development, can proceed without SOX2. Dev Biol 457:43–56
Eisen MD, Ryugo DK (2007) Hearing molecules: contributions from genetic deafness. Cell Mol Life Sci 64:566–580
Elliott KL, Pavlinkova G, Chizhikov VV, Yamoah EN, Fritzsch B (2021) Development in the mammalian auditory system depends on transcription factors. Int J Mol Sci 22:4189
Engle EC (2002) Applications of molecular genetics to the understanding of congenital ocular motility disorders. Ann N Y Acad Sci 956:55–63
Engle EC (2006) The genetic basis of complex strabismus. Pediatr Res 59:343–348
Engle EC (2007) Oculomotility disorders arising from disruptions in brainstem motor neuron development. Arch Neurol 64:633–637
Engle EC, Leigh RJ (2002) Genes, brainstem development, and eye movements. Neurology 59:304–305
Engle EC, Castro AE, Macy ME, Knoll JHM, Beggs AH (1997) A gene for isolated congenital ptosis maps to a 3cM region within 1p32-p34.1. Am J Hum Genet 60:1150–1157
Engström H, Ades HW, Hawkins JE (1964) Cytoarchitecture of the organ of Corti. Acta Otolaryngol 57:92–99
Ensfors P, Vandewater T, Loring J, Jaenisch R (1995) Complementary roles of BDNF and NT-3 in vestibular and auditory development. Neuron 14:1153–1164
Erickson SL, O’Shea KS, Ghaboosi N, Loterro L, Frantz G, Bauer M et al (1997) ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2- and neuregulin-deficient mice. Development 124:4999–5011
Erives A, Fritzsch B (2020) A screen for gene paralogies delineating evolutionary branching order of early Metazoa. G3 (Bethesda) 10:811–826
Erzurumlu RS, Murakami Y, Rijli FM (2010) Mapping the face in the somatosensory brainstem. Nat Rev Neurosci 11:252–263
Espinosa-Medina I, Saha O, Boismoreau F, Chettouch Z, Rossi F, Richardson W, Brunet J-F (2016) The sacral autonomic outflow is sympathetic. Science 354:893–897
Esteves SD, Silva AP, Coutinho MB, Abrunhosa JM, Almeida E, Sousa C (2014) Congenital defects of the middle ear—uncommon cause of pediatric hearing loss. Braz J Otolaryngol 80:251–256
Farago AF, Awatramani RB, Dymecki SM (2006) Assembly of the brainstem cochlear nuclear complex is revealed by intersectional and subtractive genetic fate maps. Neuron 50:205–218
Fariňas I, Jones KR, Tessarollo L, Vigers AJ, Huang E, Kirstein M et al (2001) Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression. J Neurosci 21:6170–6180
Feenstra I, Vissers LE, Pennings RJ, Nillessen W, Pfundt R, Kunst HP et al (2011) Disruption of teashirt zinc finger homeobox 1 is associated with congenital aural atresia in humans. Am J Hum Genet 89:813–819
Fekete DM (1999) Development of the vertebrate ear: insights from knockouts and mutants. Trends Neurosci 22:263–269
Feldman JL, McCrimmon DR (1999) Neural control of breathing. In: Zigmund MJ, Bloom FE, Landis SC, Roberts JL, Squire LR (eds) Fundamental neuroscience. Academic, San Diego, CA, pp 1063–1090
Feldman JL, Smith JC (1995) Neural control of respiratory pattern in mammals: a review. Lung Biol Health Dis 79:39–69
Fettiplace R, Hackney CM (2006) The sensory and motor roles of auditory hair cells. Nat Rev Neurosci 7:19–29
Filiano JJ, Kinney HC (1992) Arcuate nucleus hypoplasia in the sudden infant death syndrome. J Neuropathol Exp Neurol 51:394–405
Filiano JJ, Kinney HC (1994) A perspective on neuropathological findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate 65:194–197
Filiano JJ, Choi JC, Kinney HC (1990) Candidate cell populations for respiratory chemosensitive fields in the human infant medulla. J Comp Neurol 293:448–465
Filova I, Dvorakova M, Bohuslavova R, Pavlinek A, Elliott KL, Vochyanova S et al (2020) Combined Atoh1 and Neurod1 deletion reveals autonomous growth of auditory nerve fibers. Mol Neurobiol 57:5307–5323
Fitch N, Lindsay JR, Srolovitz H (1976) The temporal bone in the preauricular pit, cervical fistula, hearing loss syndrome. Ann Otol Rhinol Laryngol 85:268–275
Fletcher KT, Horrell EMW, Ayugi J, Irungu C, Muthoka M, Creel LM et al (2018) The natural history and rehabilatative outcomes of hearing loss in congenital cytomegalovirus: a systematic review. Otol Neurotol 39:854–864
Flock Å (1980) Contractile proteins in hair cells. Hear Res 2:411–412
Flock Å, Bretscher A, Weber K (1982) Immunohistochemical localization of several cytoskeletal proteins in inner ear sensory and supporting cells. Hear Res 7:75–89
Foch C, Araujo M, Weckel A, Damase-Michel C, Montastruc JL, Beneven J et al (2018) In utero drug exposure and hearing impairment in 2-year-old children. A case-control study using the EFEMERIS database. Int J Pediatr Otolaryngol 113:192–197
Fode C, Gradwohl G, Morin X, Dierich A, LeMeur M, Goridis C, Guillemot F (1998) The bHLH protein NEUROGENIN 2 is determination factor for epibranchial placode-derived sensory neurons. Neuron 20:483–494
Folgering H, Kuyper F, Kille JF (1979) Primary alveolar hypoventilation (Ondine’s curse syndrome) in an infant without external arcuate nucleus: case report. Bull Eur Physiopathol Respir 15:659–665
Fortnum HM, Summerfield AQ, Marshall DH, Davis AC, Bamford JM (2001) Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study. BMJ 323:536–540
Fowler EP (1961) Variations in the temporal bone course of the facial nerve. Laryngoscope 71:937–946
Franz H (1959) Über Gehörorgansduplikaturen. Z Laryngol Rhinol 38:16–22
Friedland DR, Eernisse R, Erbe C, Gupta N, Cioffi JA (2009) Cholesteatoma growth and proliferation: posttranscriptional regulation by microRNA-21. Otol Neurotol 30:998–1005
Friedman TB, Griffith AJ (2003) Human nonsyndromic sensorineural deafness. Annu Rev Genomics Hum Genet 4:341–402
Friedman LM, Droz AA, Avraham KB (2007) Mouse models to study inner ear development and hereditary hearing loss. Int J Dev Biol 51:609–631
Friedmann I, Arnold W (1993) Pathology of the ear. Churchill Livingstone, Edinburgh
Fritzsch B, Elliott KL (2017) Evolution and development of the inner ear efferent system: transforming a motor neuron population to connect to the most unusual motor protein via ancient nicotinic receptors. Front Cell Neurosci 11:114
Fritzsch B, Elliott KL (2018) Auditory nomenclature: combining name recognition with anatomical description. Front Neuroanat 12:99
Fritzsch B, Nichols D, Echelard Y, McMahon A (1995) Development of midbrain and anterior hindbrain ocular motoneurons in normal and Wnt-1 knockout mice. J Neurobiol 27:457–469
Fritzsch B, Silos-Santiago I, Bianchi LM, Farinas I (1997) The role of neurotrophic factors in regulating the development of inner ear development. Trends Neurosci 20:159–164
Fritzsch B, Beisel K, Jones K, Farinas L, Maklad A, Lee J et al (2002) Development and evolution of inner ear sensory epithelia and their innervation. J Neurobiol 53:143–156
Fritzsch B, Tessarollo L, Cappola E, Reichardt LF (2004) Neurotrophins in the ear: their roles in sensory neuron survival and fibre guidance. Prog Brain Res 146:265–278
Fritzsch B, Matei V, Nichlos D, Bermingham N, Jones K, Beisel K, Wang V (2005) Atoh1 null mice show directed afferent fiber growth to undifferentiated ear sensory epithelia followed by incomplete fiber retention. Dev Dyn 233:570–583
Fritzsch B, Pauley S, Beisel KW (2006) Cells, molecules and morphogenesis: the making of the vertebrate ear. Brain Res 1091:151–171
Fritzsch B, Beisel KW, Pauley S, Soukup G (2007) Molecular evolution of the vertebrate mechanosensory cell and ear. Int J Dev Biol 51:663–678
Fritzsch B, Jahan I, Pan N, Kersigo J, Duncan J, Kopecky B (2011) Dissecting the molecular basis of organ of Corti development: where are we now? Hear Res 276:16–26
Fritzsch B, Kersigo J, Yang T, Jahan I, Pan N (2016) Neurotrophic factor function during ear development: expression changes define critical phases for neuronal viability. In: Dabdoub A, Fritzsch B, Popper AN, Fay RR (eds) The primary auditory neurons of the mammalian cochlea. Springer, New York, pp 49–84
Fritzsch B, Elliott KL, Glover JC (2017) Gaskell revisited: new insights into spinal autonomics necessitate a revised motor neuron nomenclature. Cell Tissue Res 370:195–209
Fritzsch B, Elliott KL, Pavlinkova G, Duncan JS, Hansen MR, Kersigo JM (2019) Neuronal migration generates new populations of neurons that develop unique connections, physiological properties and pathologies. Front Cell Dev Biol 7:59
Fuyiyama T, Yamada M, Terao M, Terashima T, Hioki H, Inoue YU et al (2009) Inhibitory and excitatory subtypes of cochlear neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1. Development 136:2049–2058
Gasser RF (1967) The development of the facial nerve in man. Ann Otol Rhinol Laryngol 76:37–56
Gasser RF, May M (2000) Embryonic development. In: May M, Schaitkin BM (eds) The facial nerve, May’s, 2nd edn. Thieme, New York, pp 1–17
Gaufo GO, Thomas KR, Capecchi MR (2003) Hox3 genes coordinate mechanisms of genetic suppression and activation in the generation of branchial and somatic motoneurons. Development 130:5191–5201
Gavalas A, Studer M, Lumsden A, Rijli FM, Krumlauf R, Chambon P (1998) Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch. Development 125:1123–1136
Gavalas A, Ruhrberg C, Livet J, Henderson CE, Krumlauf R (2003) Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes. Development 130:5663–5679
Gerhardt HJ, Otto HD (1970) Steigbügelmissbildungen. Acta Otolaryngol (Stockholm) 70:35–44
Gerlach LM, Hutson MR, Germiller JA, Nguyen-Luu D, Victor JC, Barald KF (2000) Addition of the BMP4 antagonist, noggin, disrupts avian inner ear development. Development 127:45–54
Gillespie PG, Müller U (2009) Mechanotransduction by hair cells: models, molecules, and mechanisms. Cell 139:33–44
Glover JC, Elliott KL, Erives A, Chizhikov VV, Fritzsch B (2018) Wilhelm His’ lasting insights into hindbrain and cranial ganglia development and evolution. Dev Biol 444(Suppl 1):S14–S24
Goddard JM, Rossel M, Manley NR, Capecchi MR (1996) Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development 122:3217–3228
Gorlin RJ, Cohen MM Jr, Levin LS (1990) Syndromes of the head and neck, 3rd edn. Oxford University Press, New York, pp 666–671
Gorlin RJ, Cohen MM Jr, Hennekam RCM (eds) (2001) Syndromes of the head and neck, 4th edn. Oxford University Press, Oxford
Govaerts PJ, Cremers CWRJ, Marquet TF, Offeciers FE (1993) The persistent stapedial artery: does it prevent successful surgery? Ann Otol Rhinol Laryngol 102:724–728
Gray PA (2008) Transcription factors and the genetic organization of brainstem respiratory neurons. J Appl Physiol 104:1513–1521
Gray PA (2013) Transcription factors define the neuroanatomical organization of the medullary reticular formation. Front Neuroanat 7:7
Gray PA, Hayes JA, Ling GY, Llona I, Nivasan T, Picardo MD et al (2010) Developmental origin of preBötzinger complex respiratory neurons. J Neurosci 30:14883–14895
Gross MK, Dottori M, Goulding M (2002) Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron 34:535–549
Groves AK, Bronner-Fraser M (2000) Competence, specification and commitment in otic placode induction. Development 127:3489–3499
Groves AK, Fekete DM (2012) Shaping sound in space: the regulation of inner ear patterning. Development 139:245–257
Guthrie S (1996) Patterning the hindbrain. Curr Opin Neurobiol 6:41–48
Guthrie S (2007) Patterning and axon guidance of cranial motor neurons. Nat Rev Neurosci 8:859–871
Gutowski NJ, Bosley TM, Engle E (2003) Workshop Report 110th ENMC International Workshop: the congenital cranial dysinnervation disorders (CCDDs). Neuromuscul Disord 13:573–578
Guyenet PG (2000) Neural structures that mediate sympathoexcitation during hypoxia. Resp Physiol 121:147–162
Guyenet PG, Stornetta RL, Bayliss DA (2008) Retrotrapezoid nucleus and central chemoreception. J Physiol 586:2043–2048
Hamilton WJ, Mossman HW (1972) Hamilton, Boyd and Mossman’s Human Embryology. Prenatal development of form and function, 4th edn. Heffer, Cambridge
Hanson JR, Anson BJ, Strickland EM (1962) Branchial sources of the auditory ossicles in man. Arch Otolaryngol 76:100–122, and 200–215
Harding BN (2018) Brainstem malformations. In: Adle-Biassette H, Harding BN, Golden JA (eds) Developmental neuropathology, 2nd edn. Wiley, Hoboken, NJ, pp 167–171
Harding BN, Vossough A, Goldberg E, Santi M (2016) Pontine tegmental cap dysplasia: neuropathological confirmation of a rare clinical/radiological syndrome. Neuropathol Exp Neurobiol 42:301–306
Hardy JB (1973) Fetal consequences of maternal viral infections in pregnancy. Arch Otolaryngol 98:218–227
Hartel BP, Löfgren M, Huygen PL, Guchelaar I, Lo-A-Njoe Kort N, Sadeghi AM et al (2016) A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa. Hear Res 339:60–68
Heidary G, Traboulsi EI, Engle EC (2012) The genetics of strabismus and associated disorders. In: Traboulsi EI (ed) Genetic diseases of the eye. Oxford University Press, Oxford New York, pp 657–686
Herbarth B, Pingault V, Bondurand N, Kuhlbrodt K, Hermans-Borgmeyer I, Puliti A et al (1998) Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschsprung disease. Proc Natl Acad Sci U S A 95:5161–5165
Hernandez-Miranda LR, Müller T, Birchmeier C (2017) The dorsal spinal cord and hindbrain: from developmental mechanisms to functional circuits. Dev Biol 432:34–42
Hertzano R, Montcouquiel M, Rashi-Elkeles S, Elkon R, Yücel R, Frankel WN et al (2004) Transcription-profiling of inner ear from Pou4f3 (ddl/ddl) identifies Gli1 as a target of Pou4f3 deafness gene. Hum Mol Genet 13:2143–2153
Hilgert N, Smith RJ, Van Camp G (2009) Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in the DNA diagnosis? Mutat Res 681:189–196
Hinrichsen KV (1990) Peripheres Nervensystem. In: Hinrichsen KV (ed) Humanembryologie. Springer Verlag, Berlin Heidelberg New York, pp 449–475
His W Jr (1889) Zur Entwicklungsgeschichte des Acustico-Facialisgebietes beim Menschen. Arch Anat Physiol, Anat Abt, Suppl:1–28
Hochstetter F (1948) Entwicklungsgeschichte der Ohrmuschel und des äusseren Gehörganges des Menschen. Denkschr Akad Wiss Wien Math-Naturwiss Kl 108:1–50
Holme RH, Steel KP (1999) Genes involved in deafness. Curr Opin Genet Dev 9:309–314
Holzinger A, Mittal RA, Kachel W, Priesmann H, Hammel M, Ihrler S et al (2005) A novel 17 bp deletion in the PHOX2B gene causes congenital central hypoventilation syndrome with total aganglionosis of the small and large intestine. Am J Med Genet 139A:50–51
Holzschuh J, Hauptmann G, Driever W (2003) Genetic analysis of the roles of Hh, FGF8, and nodal signaling during catecholaminergic system development in the zebrafish brain. J Neurosci 23:5507–5519
Honings J, Pennings RJE, Hoefsloot LH, Joosten FPM, Cremers CWRJ (2008) Head trauma of eliciting event in transient deterioration of sensorineural hearing loss and vertigo in Pendred/EVA syndrome. Int J Med Otorhinolaryngol 3:177–181
Horn AKE, Straka H (2021) Functional organization of extraocular motoneurons and eye muscles. Annu Rev Vision Sci 7:793–825
Hotchkiss MG, Miller NR, Clark AW, Green WR (1980) Bilateral Duane’s retraction syndrome: a clinico-pathologic case report. Arch Ophthalmol 98:870–874
Hoth CF, Milunsky A, Lipsky N, Sheffer R, Clarren SK, Baldwin CT (1993) Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I). Am J Hum Genet 53:455–462
House HP, Patterson ME (1964) Persistent stapedial artery: report of two cases. Trans Am Acad Ophthalmol Otolaryngol 68:644–646
Hunter AGW, Yotsuyanagi T (2005) The external ear: more attention to detail may aid syndrome diagnosis and contribute answers to embryological questions. Am J Med Genet 135A:237–250
Hunter A, Frias JL, Gillessen-Kaesbach G, Hughes H, Jones K, Wilson L (2009) Elements of morphology: standard terminology for the ear. Am J Med Genet Part A 149A:40–60
Igarashi Y, Ishii T (1980) Embryonic development of the human organ of Corti: electron microscopic study. Int J Paediatr Otorhinolaryngol 2:51–62
Irving C, Mason I (2000) Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression. Development 127:177–188
Iskusnykh I, Steshina EY, Chizhikov VV (2016) Ptf1a leads to a widespread cell-fate misspecification in the brainstem, affecting the development of somatosensory and viscerosensory nuclei. J Neurosci 36:2691–2719
Ito T, Choi BY, King KA, Zalewski CK, Mushett J, Chattaraj P et al (2011) SLC26A4 genotypes and phenotypes associated with enlargement of the vestibular aqueduct. Cell Physiol Biochem 28:545–552
Ivanova A, Yuasa S (1998) Neuronal migration and differentiation in the development of the mouse dorsal cochlear nucleus. Dev Neurosci 20:495–511
Iyer AA, Groves AK (2021) Transcription factor reprogramming in the inner ear: turning on cell fate switches to regenerate sensory hair cells. Front Cell Neurosci 15:660748
Jackler RK, Luxford WM, House WF (1987) Congenital malformations of the inner ear: a classification based on embryogenesis. Laryngoscope 97(Suppl 40):2–14
Jacobs MJ (1970) The development of the human motor trigeminal complex and accessory facial nucleus and their topographic relations with the facial and abducens nuclei. J Comp Neurol 138:161–194
Jacobs J, Guthrie S (2000) Facial visceral motor neurons display specific rhombomere origin and axon pathfinding behavior in the chick. J Neurosci 20:7664–7671
Jahan I, Pan N, Kersigo J, Fritzsch B (2010) Neurod1 suppresses hair cell differentiation in ear ganglia and regulates hair cell subtype development in the cochlea. PLoS One 5:e11661
Jahan I, Pan N, Kersigo J, Fritzsch B (2013) Beyond generalized hair cells: molecular cues for hair cell types. Hear Res 297:30–41
Jahan I, Elliott KL, Fritzsch B (2018) Understanding molecular evolution and development of the organ of Corti can provide clues for hearing restoration. Integr Comp Biol 58:351–365
Jahan I, Kersigo J, Elliott KL, Fritzsch B (2021) Smoothened overexpression causes trochlear motoneurons to reroute and innervate ipsilateral eyes. Cell Tissue Res 384:59–72
Jen J, Coulin C, Bosley TM, Salih MAM, Sabatti C, Nelson SF, Baloh RW (2002) Familial horizontal gaze with progressive scoliosis (HGPS) maps to chromosome 11q23-25. Neurology 59:432–435
Jen J, Chan W-M, Bosley TM, Wan J, Carr JR, Rüb U et al (2004) Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science 304:1509–1513
Jessell TM (2000) Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 1:20–29
Jissendi-Tchofo P, Doherty D, McGillivray G, Hevner R, Shaw D, Ishak G et al (2009) Pontine tegmental cap dysplasia: mR imaging and diffusion tensor imaging features of impaired navigation. AJNR Am J Neuroradiol 30:113–119
Jissendi-Tchofo P, Severino M, Nguema-Edzang B, Toure C, Soto Ares G, Barkovich AJ (2015) Update on neuroimaging phenotypes of mid-hindbrain malformations. Neuroradiology 57:113–138
Johansson B, Wedenberg E, Weston B (1964) Measurement of tone response by the human fetus. Acta Otolaryngol 57:188–192
Johnson JM, Moonis G, Green GE, Carmody R, Burbank HN (2011a) Syndromes of the first and second branchial arches, Part 1: embryology and characteristic defects. AJNR Am J Neuroradiol 32:14–19
Johnson JM, Moonis G, Green GE, Carmody R, Burbank HN (2011b) Ibid, Part 2: syndromes. AJNR Am J Neuroradiol 32:230–237
Joyner AL (1996) Engrailed, Wnt and Pax genes regulate midbrain-hindbrain development. Trends Genet 12:15–20
Joyner AL (2002) Establishment of anterior-posterior and dorsal-ventral pattern in the early central nervous system. In: Rossant J, Tam PPL (eds) Mouse development. Patterning, morphogenesis, and organogenesis. Academic, San Diego, CA, pp 107–126
Kalatzis V, Sahly I, El-Amraoui A, Petit C (1998) Eya1 expression in the developing ear and kidney: towards the understanding of the pathogenesis of Branchio-Oto-Renal (BOR) syndrome. Dev Dyn 213:486–499
Kalia M, Mesulam M-M (1980) Brainstem projections of sensory and motor components of the vagus complex in the cat. II. Laryngeal, tracheobronchial, pulmonary, cardiac and gastrointestinal branches. J Comp Neurol 193:467–508
Kanagasuntheram R (1967) A note on the development of the tubotympanic recess in the human embryo. J Anat (Lond) 101:731–741
Kang BJ, Chang DA, Mackay DD, West GH, Moreira TS, Takakura AC et al (2007) Central nervous system distribution of transcriptional factor Phox2a in the adult rat. J Comp Neurol 505:627–641
Karis A, Pata I, van Doorninck JH, Grosveld F, de Zeeuw CI, de Caprona D, Fritzsch B (2001) Transcription factor GATA-3 alters pathway selection of olivocochlear neurons and affects morphogenesis of the ear. J Comp Neurol 429:615–630
Karmody CS, Annino DJ Jr (1995) Embryology and anomalies of the external ear. Facial Plast Surg 11:251–256
Keats BJB, Corey DP (1999) The Usher syndromes. Am J Med Genet 89:158–166
Kemperman MH, Stinckens C, Kumar S, Huygen PLM, Joosten FBM, Cremers CWRJ (2001) Progressive, fluctuant hearing loss, an enlarged vestibular aqueduct and cochlear hypoplasia in the BOR syndrome. Otol Neurotol 22:637–643
Kemperman MH, Stinckens C, Kumar S, Joosten FBM, Huygen PLM, Cremers CWRJ (2002a) The branchio-oto-renal syndrome. Adv Otorhinolaryngol 61:192–200
Kemperman MH, Koch SMP, Joosten FBM, Kumar S, Huygen PLM, Cremers CWRJ (2002b) Inner ear anomalies are frequent but non-obligatory features of the branchio-oto-renal syndrome. Arch Otolaryngol Head Neck Surg 128:1033–1038
Kemperman MH, Hoefsloot LH, Cremers CWRJ (2002c) Hearing loss and connexin 26. J Roy Soc Med 95:171–177
Kersigo J, D’Angelo A, Gray BD, Soukup GA, Fritzsch B (2011) The role of sensory organs and the forebrain for the development of the craniofacial shape as revealed by Foxg1-‘cre’- mediated microRNA loss. Genesis 49:326–341
Khan AO (2022a) Duane retraction syndrome. In: Black GCM, Ashworth JL, Sergouniotis PI (eds) Clinical genetics and genomics. Academic Press, London, pp 412–417
Khan AO (2022b) Horizontal gaze palsy and progressive scoliosis. In: Black GCM, Ashworth JL, Sergouniotis PI (eds) Clinical genetics and genomics. Academic Press, London, pp 418–421
Khateb S, Kowalowski B, Bedoni N, Damme M, Pollack N, Saada A et al (2018) A homozygous founder missense variation arylsulfatase G abolishes its enzymatic activity causing atypical Usher syndrome in humand. Genet Med 20:1004–1009
Kiernan AE, Steel KP, Fekete DM (2002) Development of the mouse inner ear. In: Rossant J, Tam PPL (eds) Mouse development. Patterning, morphogenesis, and organogenesis. Academic, San Diego, CA, pp 539–566
Kiernan AE, Pelling AL, Leung KK, Tang AS, Bell DM, Tease C et al (2005) Sox2 is required for sensory organ development in the mammalian inner ear. Nature 434:1031–1035
Kikkawa Y, Seki Y, Okumura K, Ohshiba Y, Miyasaki Y, Suzuki S et al (2012) Advantages of a mouse model for human hearing impairment. Exp Anim 61:85–98
Kim H-N, Kim YH, Park IY, Kim GR, Chung IH (1990) Variability of the surgical anatomy of the neurovascular complex of the cerebellopontine angle. Ann Otol Rhinol Laryngol 99:288–295
Kim WY, Fritzsch B, Serls A, Bakel LA, Huang EJ, Reichardt LF et al (2001) NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development. Development 128:417–426
Kimberling WJ (2004) Genetic hearing loss associated with eye disorders. In: Toriello HV, Reardon W, Gorlin RJ (eds) Hereditary hearing loss and its syndromes, 2nd edn. Oxford University Press, Oxford, pp 126–165
Kimberling WJ, Möller C (1995) Clinical and molecular genetics of Usher syndrome. J Am Acad Audiol 6:63–72
Kimura RS (1975) The ultrastructure of the organ of Corti. Int Rev Cytol 42:173–222
Kinney HC, Filiano JJ, Harper RM (1992) The neuropathology of the sudden infant death syndrome. A review. J Neuropathol Exp Neurol 51:115–126
Kinney HC, Hefti MM, Goldstein RB, Haynes RL (2018) Sudden infant death syndrome. In: Adle-Biassette H, Harding BN, Golden JA (eds) Developmental neuropathology, 2nd edn. Wiley, Hoboken, NJ, pp 269–280
Klingbeil KD, Greenland CM, Arslan S, Llamos Paneque A, Gurkan H, Demir Ulusal S et al (2017) Novel EYA1 variants causing branchio-oto-renal syndrome. Int J Pediatr Otolaryngol 98:59–63
Kohlhase J, Heinrich M, Schubert L, Liebers M, Kispert A, Laccone F et al (2002) Okihiro syndrome is caused by SAL1A mutations. Hum Mol Genet 11:2979–2987
Kopecky B, Fritzsch B (2013) Embryology of the mammalian ear. In: Toriello HV, Smith SD (eds) Hereditary hearing loss and its syndromes, 2nd edn. Oxford University Press, New York, pp 13–57
Korver AM, Smith RJ, Van Camp G, Schleiss MR, Bitner-Glindzicz MA, Lustig LR et al (2017) Congenital hearing loss. Nat Rev Disease Primers 3:1–17
Kösling S, Omenzetter M, Bartel-Friedrich S (2009) Congenital malformations of the external and middle ear. Eur J Radiol 69:269–279
Kremer H (2019) Hereditary hearing loss; about the known and the unknown. Hear Res 376:58–68
Kremer H, Kuyt LP, van den Helm B, van Reen M, Leunissen JAM, Hamel BC et al (1996) Localization of a gene for Möbius syndrome to chromosome 3q by linkage analysis in a Dutch family. Hum Mol Genet 5:1367–1371
Kremer H, van Wijk E, Märker T, Wolfrum U, Roepman R (2006) Usher syndrome: molecular links of pathogenesis, proteins and pathways. Hum Mol Genet 15(Spec No 2):R262–R270
Krug P, Moriniere V, Marlin S, Koubi V, Gabriel HD, Colin E et al (2011) Mutations screening of the EYA1, SIX1 and SIX5 genes in a large cohort of patients harboring branchio-oto-renal syndrome calls into question the pathogenetic role of SIX5 mutations. Hum Mutat 32:183–190
Krumlauf R (1994) Hox genes in vertebrate development. Cell 78:191–201
Kuemerle B, Zanjani H, Joyner A, Herrup K (1997) Pattern deformities and cell loss in Engrailed-2 mutant mice suggest two separate patterning events during cerebellar development. J Neurosci 17:7881–7889
Kuhlman KA, Burns KA, Depp R, Sabbagha RE (1988) Ultrasound imaging of normal fetal response to external vibratory acoustic stimulation. Am J Obstet Gynecol 158:47–51
Kumar D (1990) Moebius syndrome. J Med Genet 27:122–126
Lai HC, Seal RP, Johnson JE (2016) Making sense out of spinal cord somatosensory development. Development 143:3434–3448
Lammens M, Moerman P, Fryns JP, Schröder JM, Spinnewyn D, Casaer P, Dom R (1998) Neuropathological findings in Moebius syndrome. Clin Genet 54:136–141
Lavezzi AM, Matturi L (2008) Functional neuroanatomy of the human pre-Bötzinger complex with particular reference to sudden unexplained perinatal and infant death. Neuropathology 28:10–16
Lecanuet J-P, Schaal B (1996) Fetal sensory competencies. Eur J Obstet Gynecol 68:1–23
Lee KJ, Jessell TM (1999) The specification of dorsal fates in the vertebrate central nervous system. Annu Rev Neurosci 22:261–294
Lee K-F, Simon H, Chen H, Bates B, Hung M-C, Hauser C (1995) Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature 378:394–398
Lee SM, Danielian PS, Fritzsch B, McMahon AP (1997) Evidence that FGF8 signalling from the midbrain-hindbrain junction regulates growth and polarity in the developing midbrain. Development 124:959–969
Lee KJ, Dietrich P, Jessell TM (2000) Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification. Nature 403:734–740
Lee S-Y, Yoo HS, Han JH, Lee DH, Park SS, Suh MH et al (2022) Novel molecular genetic etiology of asymmetric hearing loss: aurosomal-dominant LMX1A variants. Ear Hearing 43(6):1698–1707
Leigh R, Zee D (1999) The neurology of eye movements, 3rd edn. Oxford University Press, New York
LeMasurier M, Gillespie PG (2005) Hair-cell mechanotransduction and cochlear amplification. Neuron 48:403–415
Lemire RJ, Loeser JD, Leech RW, Alvord EC Jr (1975) Normal and abnormal development of the human nervous system. Harper & Row, Hagerstown, MD
Lemire RJ, Beckwith JB, Warkany J (1978) Anencephaly. Raven, New York
Lengyel D, Zaunbauer W, Keller E, Gottlob I (2000) Möbius syndrome: MRI findings in three cases. J Pediatr Ophthalmol Strabismus 37:305–308
Leong S, Ashwell KW (1997) Is there a zone of vascular vulnerability in the fetal brainstem? Neurotoxicol Teratol 19:265–275
Li S, Price SM, Cahill H, Ryugo DK, Shen MM, Xiang M (2002) Hearing loss caused by progressive degeneration of cochlear hair cells in mice deficient for the Barhl1 homeobox gene. Development 129:3523–3532
Libby RT, Steel KP (2000) The roles of unconventional myosins in hearing and deafness. Essays Biochem 35:159–174
Liberman MC, Rosowski JJ, Lewis RF (2010) Physiology and pathophysiology. In: Merchant SN, Nadol JB Jr (eds) Schuknecht’s pathology of the ear, 3rd edn. People’s Medical Publishing House—USA, Shelton, CT, pp 97–134
Liebreich R (1861) Abkunft und Ehen unter Blutsverwandten als Grund von Retinitis pigmentosa. Dtsch Klin 13:53–55
Liem KF, Tremml G, Jessell TM (1997) A role for the roof plate and its resident TGF beta-related proteins in neuronal patterning in the dorsal spinal cord. Cell 91:127–138
Lim DJ (1980) Cochlear anatomy related to cochlear micromechanics. A review. J Acoust Soc Am 67:1686–1695
Lim DJ (1986) Functional structure of the organ of Corti: a review. Hear Res 22:117–146
Lin Z, Cantos R, Potente M, Wu DK (2005) Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling. Development 132:2309–2318
Lipski J, Merrill EG (1980) Electrophysiological demonstration of the projection of expiratory neurons in the rostral medulla to contralateral dorsal respiratory group. Brain Res 197:521–524
Liu A, Joyner AL (2001) Early anterior/posterior patterning of the midbrain and cerebellum. Annu Rev Neurosci 24:869–896
Liu M, Pereira FA, Price SD, Chu M-J, Shope C, Himes D et al (2002) Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems. Genes Dev 14:2839–2854
Lowenstein ED, Cui K, Hernandez-Miranda LR (2022) Regulation of early cerebellar development. FEBS J
Lu DC, Niu T, Alaynick WA (2015) Molecular and cellular development of spinal cord locomotor circuitry. Front Mol Neurosci 8:25
Lumsden A (1990) The cellular basis of segmentation in the developing hindbrain. Trends Neurosci 13:329–335
Lumsden A (2004) Segmentation and compartition in the early avian hindbrain. Mech Dev 121:1081–1088
Lumsden A, Keynes R (1989) Segmental patterns of neuronal development in the chick hindbrain. Nature 337:424–428
Lumsden A, Krumlauf R (1996) Patterning the vertebrate neuraxis. Science 274:1109–1115
Lunde A, Okaty BW, Dymecki SM, Glover JC (2019) Molecular profiling defines evolutionary conserved transcription factor signatures of major vestibulospinal neuron groups. eNeuro6:e0475
Luquetti DV, Heike CL, Hing AV, Cunnigham ML, Cox TC (2012) Microtia: epidemiology and genetics. Am J Med Genet A 158A:124–139
Ma Q, Chen ZF, Del Braco BI, De la Pompe JL, Anderson DJ (1998) neurogenin 1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia. Neuron 20:469–482
Ma Q, Anderson DJ, Fritzsch B (2000) Neurogenin 1 null mutant ears develop fewer, morphologically normal hair cells in smaller sensory epithelia devoid of innervation. J Assoc Res Otolaryngol 1:129–143
Macova I, Pysanenko K, Chumak T, Dvorakova M, Bohuslavova R, Syka J et al (2019) Neurod1 is essential for the primary tonotopic organization and related auditory information processing in the midbrain. J Neurosci 39:984–1004
Mamourian A, Miller G (1994) Neonatal pontomedullary disconnection with aplasia or destruction of the lower brain stem: a case of pontoneocerebellar hypoplasia? AJNR Am J Neuroradiol 15:1483–1485
Mann IC (1927) The developing third nerve nucleus in human embryos. J Anat (Lond) 61:424–438
Mansour SL, Goddard JM, Capecchi MR (1993) Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear. Development 117:13–28
Maricich SM, Xia A, Mathes EL, Wang VY, Oghalai JS, Fritzsch B et al (2009) Atoh-1 lineal neurons are required for hearing, and for the survival of neurons in the spiral ganglion and brainstem accessory auditory nuclei. J Neurosci 29:11123–11133
Marín F, Puelles L (1994) Patterning of the embryonic avian midbrain after experimental inversions: a polarizing activity from the isthmus. Dev Biol 163:19–37
Marquet JF, Declau FR, De Cock M (1988) Congenital middle ear malformations. Acta Otorhinolaryngol Belg 42:117–302
Martínez S, Wassef M, Alvarado-Mallart RM (1991) Induction of a mesencephalic phenotype in the 2-day-old chick prosencephalon is preceded by the early expression of the homeobox gene En. Neuron 6:971–981
Martínez S, Puelles E, Puelles L, Echevarria D (2012) Molecular regionalization of the developing neural tube. In: Watson C, Paxinos G, Puelles L (eds) The mouse nervous system. Elsevier, Amsterdam, pp 2–18
Mastick GS, Fan C-M, Tessier-Lavigne M, Serbedzija GN, McMahon AP, Easter SS Jr (1996) Early detection of neuromeres in Wnt-1−/− mutant mice: evaluation by morphological and molecular markers. J Comp Neurol 374:246–258
Matei V, Pauley S, Kaing S, Rowitch D, Beisel KW, Morris K et al (2005) Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit. Dev Dyn 234:633–650
Matturi L, Biondo B, Mercurio P, Rossi L (2000) Severe hypoplasia of medullary arcuate nucleus. Quantitative analysis in sudden infant death syndrome. Acta Neuropathol (Berl) 99:371–375
Matturi L, Biondo B, Suárez-Mier MP, Rossi L (2002) Brain stem lesions in the sudden infant death syndrome: variability in the hypoplasia of the arcuate nucleus. Acta Neuropathol (Berl) 104:12–20
May M, Schaitkin BM (eds) (2000) The facial nerve, May’s, 2nd edn. Thieme, New York
Maynard TM, Zohm IE, Moody SA, LaMantia A-S (2020) Suckling, feeding, and swallowing: behaviors, circuits, and targets for neurodevelopmental pathology. Annu Rev Neurosci 43:315–336
McGuirt WT, Prasad SD, Griffith AJ, Kunst HP, Green GE, Shpargel KB, Runge C et al (1999) Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13). Nat Genet 23:413–419
McKay IJ, Lewis J, Lumsden A (1997) Organization and development of facial motor neurons in the Kreisler mutant mouse. Eur J Neurosci 9:1499–1506
McMahon AP, Joyner AL, Bradley A, McMahan JA (1992) The midbrain-hindbrain phenotype of Wnt-1-/Wnt-1- mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum. Cell 69:581–595
Mellinger JF, Gomez MR (1987) Agenesis of the cranial nerves. Handb Clin Neurol 50:211–223
Mencía A, Modamio-Høybjør S, Redshaw N, Morín N, Mayo-Merino F, Olavarrieto L et al (2009) Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat Genet 41:609–613
Merchant SN (2010) Genetically determined and other developmental defects. In: Merchant SN, Nadol JB Jr (eds) Schuknecht’s pathology of the ear, 3rd edn. People’s Medical Publishing House—USA, Shelton, CT, pp 137–277
Merchant SN, Nadol JB Jr (eds) (2010) Schuknecht’s pathology of the ear, 3rd edn. People’s Medical Publishing House—USA, Shelton, CT
Merio GR, Paleari L, Mantero S, Zerega B, Adamska M, Rinkwitz S et al (2002) The Dlx5 homeobox gene is essntial for vestibular morphogenesis in the mouse embryo througha BMP4-mediated pathway. Dev Biol 248:157–169
Meyer D, Birchmeier C (1995) Multiple essential functions of neuregulin in development. Nature 378:386–390
Michalski N, Petit C (2019) Genes involved in the development and physiology of both the peripheral and central auditory systems. Annu Rev Neurosci 42:67–86
Michel EM (1863) Mémoire sur les anomalies congénitales de l’oreille interne. Gaz Méd Strasb 3:55–58
Millen KJ, Wurst W, Herrup K, Joyner AL (1994) Abnormal embryonic cerebellar development and patterning of postnatal foliation in two mouse Engrailed-2 mutants. Development 120:695–706
Miller NR, Kiel SM, Green WR, Clark AW (1982) Unilateral Duane’s retraction syndrome (type 1). Arch Ophthalmol 100:1468–1472
Milo M, Cacciabue-Rivolta D, Kneebone A, Van Doorninck H, Johnson C, Lawoko-Kerali G et al (2009) Genomic analysis of the function of the transcription factor gata3 during development of the mammalian inner ear. PLoS One 4:e7144
Mishima Y, Lindgren AG, Chizhikov VV, Johnson RL, Miller KJ (2009) Overlapping function of Lmx1a and Lmx1b in anterior hindbrain roof plate formation and cerebellar growth. J Neurosci 29:11377–11384
Mittal R, Liu G, Polineni SP, Bencir N, Yan D, Liu XZ (2019) Role of microRNAs in inner ear development and hearing loss. Gene 686:49–55
Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan WM et al (2008) Human CHN1 mutations hyperactivate alpha2-chimaerin and cause Duane’s retraction syndrome. Science 321:839–843
Möbius PJ (1888) Über angeborene doppelseitige Abducens-Facialis-Lähmung. Münch Med Wochenschr 35:91–94
Moens CB, Prince VE (2002) Constructing the hindbrain: insights from the zebrafish. Dev Dyn 224:1–17
Mondini C (1791) Anatomia surdi nedi sectio. De Bononiensii Scientarum et Artium Instituto Atque Academi Commentarii. Bologna, pp 419-431
Moore JK, Linthicum FH Jr (2004) Auditory system. In: Paxinos G, Mai JK (eds) The human nervous system, 2nd edn. Elsevier, Amsterdam, pp 1241–1279
Moore JK, Linthicum FH Jr (2007) The human auditory system: a timeline of development. Int J Audiol 46:460–478
Moore JK, Osen KK (1979) The cochlear nuclei in man. Am J Anat 154:393–418
Moore JK, Perazzo LM, Braun A (1995) Time course of axonal myelination in the human brainstem auditory pathway. Hear Res 87:21–31
Moore JK, Guan Y-L, Shi S-R (1997) Axogenesis in the human fetal auditory system, demonstrated by neurofilament immunohistochemistry. Anat Embryol (Berl) 195:15–30
Moore JK, Simmons DD, Guan Y-L (1999) The human olivocerebellar system: organization and development. Audiol Neurootol 4:311–325
Morin X, Cremer H, Hirsch M-R, Kapur RP, Gotidis C, Brunet J-F (1997) Defects in sensory and autonomic ganglia and absence of locus coeruleus in mice deficient for the homeobox gene Phox2a. Neuron 18:411–423
Morris JK, Maklad A, Haasen LA, Feng F, Sorensen C, Lee KF et al (2006) A disorganized innervation of the inner ear persists in the absence of ErbB2. Brain Res 1091:186–199
Morsli H, Tuorto F, Choo D, Postiglione MP, Simeone A, Wu DK (1999) Otx1 and Otx2 activities are required for the normal development of the mouse inner ear. Development 126:2335–2343
Morton CC, Nance WE (2006) Newborn hearing screening—a silent revolution. N Engl J Med 354:2151–2164
Müller F, O’Rahilly R (1983) The first appearance of the major divisions of the human brain at stage 9. Anat Embryol (Berl) 168:419–432
Müller F, O’Rahilly R (1990) The human rhombencephalon at the end of the embryonic period proper. Am J Anat 189:127–145
Müller T, Brohmann H, Oierani A, Heppenstall PA, Lewin GR, Jessell TM, Birchmeier C (2002) The homeodomain factor Lbx1 distinguishes two major programms of neuronal differentiation in the distal spinal cord. Neuron 34:551–562
Müller M, Jabs N, Lorke DE, Fritzsch B, Sander M (2003) Nkx6.1 controls migration and axon pathfinding of cranial branchio-motoneurons. Development 130:5815–5826
Mustapha M, Weil D, Chardemour S, Elias S, El-Zir E, Beckmann JS et al (1999) An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness DFNB21. Hum Mol Genet 8:409–412
Nager FR (1927) Zur Histologie der Taubstummheit bei Retinitis pigmentosa. Beitr Pathol Anat 77:288–303
Nager FR (1952) Histologische Ohruntersuchungen bei Kindern nach mütterlicher Rubella. Pract Otorhinolaryngol 14:337–359
Nager GT, Levin LS (1980) Congenital aural atresia: embryology, pathology, classification, genetics, and surgical management. In: Paparella MM, Shumrick DA, Meyerhoff WL, Seid AB (eds) Otolaryngology, 2nd edn. Saunders, Philadelphia, PA, pp 1303–1344
Nakamura H (2001) Regionalization of the optic tectum: combinations of gene expression that define the tectum. Trends Neurosci 24:32–39
Nakamura H, Watanabe Y (2005) Isthmus organizer and regionalization of the mesencephalon and metencephalon. Int J Dev Biol 49:231–235
Nakano M, Yamada K, Fain J, Sener EC, Selleck CJ, Awad AH et al (2001) Homozygous mutations in ARIX (PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. Nat Genet 29:315–320
Nara T, Goto N, Nakae Y, Okada A (1993) Morphometric development of the human auditory system: ventral cochlear nucleus. Early Hum Dev 32:93–102
Nara T, Goto N, Hamano S-I, Okada A (1996) Morphometric development of the human fetal auditory system: inferior collicular nucleus. Brain Res 18:35–39
Nattie EE (1999) CO2 brain stem chemoreceptors and breathing. Prog Neurobiol 59:299–331
Nichols DH, Bruce LL (2006) Migratory routes and fates of cells transcribing the Wnt-1 gene in the murine hindbrain. Dev Dyn 235:285–300
Nichols DH, Pauley S, Jahan I, Beisel KW, Millen KJ, Fritzsch B (2008) Lmx1a is required for segregation of sensory epithelia and normal ear histogenesis and morphogenesis. Cell Tissue Res 334:339–358
Nichols D, Bouma J, Kopecky B, Jahan I, Beisel KW, He D et al (2020) Interaction with ectopic cochlear crista sensory epithelia disrupts basal cochlear sensory epithelium development in Lmx1a mutant mice. Cell Tissue Res 380:435–448
Nie L (2008) KCNQ4 mutations associated with nonsyndromic progressive sensorineural hearing loss. Curr Opin Otolaryngol Head Neck Surg 16:441–444
Nieuwenhuys R (1984) Anatomy of the auditory pathways, with emphasis on the brain stem. Adv Otorhinolaryngol 34:25–38
Nieuwenhuys R, Voogd J, van Huijzen C (1988) The human central nervous system, 3rd edn. Springer, Berlin Heidelberg New York
Nishikori T, Hatta T, Kawauchi H, Otani H (1999) Apoptosis during inner ear development in human and mouse embryos: an analysis by computer-assisted three-dimensional reconstruction. Anat Embryol (Berl) 200:19–26
Nishimura Y, Kumoi T (1992) The embryonic development of the human external auditory meatus. Preliminary report. Acta Otolaryngol 112:496–503
Nishio SY, Hatton M, Moteki H, Tsukada K, Miyagawa M, Naito T et al (2015) Gene expression profiles of the cochlea and vestibular endorgans: localization and function of genes causing deafness. Ann Otol Rhinol Laryngol 124(Suppl 1):6S–48S
Norman MG, McGillivray BC, Kalousek DK, Hill A, Poskitt KJ (1995) Congenital malformations of the brain. Pathologic, embryologic, clinical, radiologoc and genetic aspects. Oxford University Press, New York
Nothwang HG (2016) Evolution of mammalian sound localization circuits: a developmental perspective. Prog Neurobiol 141:1–24
O’Rahilly R (1983) The timing and sequence of events in the development of the human eye and ear. Anat Embryol (Berl) 168:87–99
O’Rahilly R, Müller F (2001) Human embryology & teratology, 3rd edn. Wiley-Liss, New York
Okumura A, Lee T, Shimojima K, Hisata K, Shoji H, Takanashi J et al (2009) Brainstem disconnection associated with nodular heterotopia and proatlantal arteries. Am J Med Genet Part A 149A:2479–2483
Omichi R, Shibata SB, Morton CC, Smith RJ (2019) Gene therapy for hearing loss. Hum Mol Genet 28(R1):R65–R79
Onimura H, Ikeda K, Kawakami K (2008) CO2—sensitive presinspiratory neurons of the parafacial rspiratory group express Phox2b in the neonatal rat. J Neurosci 28:12845–12850
Oystreck DT, Engle EC, Bosley TM (2011) Recent progress in understanding congenital cranial dysinnervation disorders. J Neuroophthalmol 31:69–77
Pan N, Jahan I, Lea JE, Fritzsch B (2009) Defects in the cerebella of conditional Neurod1 null mice correlate with effective T9 (Atoh1-cre) recombination and granule cell requirements for Neurod1 for differentiation. Cell Tissue Res 337:407–428
Pan N, Jahan I, Kersigo J, Kopecky B, Santi P, Johnson S et al (2010) Conditional deletion of Atoh1 using Pax2-Cre results in viable mice without differentiated cochlear hair cells that have lost most of the organ of Corti. Hear Res 275:66–80
Pan N, Jahan I, Kersigo J, Duncan JS, Kopecky B, Fritzsch B (2012a) A novel Atoh1 ‘self-terminating’ mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability. PloS One:e30358
Pan N, Kopecky B, Jahan I, Fritzsch B (2012b) Understanding the evolution and development of neurosensory transcription factors of the ear to enhance therapeutic translation. Cell Tissue Res 349:415–432
Pan B, Geleoc GS, Asai Y, Horwitz G, Kurima K, Ishikawa K et al (2013) TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear. Neuron 79:504–515
Pappas DG (1983) Hearing impairments and vestibular abnormalities among children with subclinical cytomegalovirus. Ann Otol Rhinol Laryngol 92:552–557
Parisi MA, Dobyns WB (2003) Human malformations of the midbrain and hindbrain: review and proposed classification scheme. Mol Genet Metab 80:36–53
Park JG, Tischfield MA, Nugent AA, Cheng L, Di Gioia SA, Chan WM et al (2016) Loss of MAFB function in humans and mice causes Duane syndrome, aberrant extraocular muscle innervation, and inner-ear defects. Am J Hum Genet 98:1220–1227
Parker HJ, Krumlauf R (2020) A Hox gene regulatory network for hindbrain segmentation. Curr Top Dev Biol 139:169–203
Parr BR, Shen MJ, Vassilova G, McMahon AP (1993) Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development 119:247–261
Pasini A, Wilkinson DG (2002) Stabilizing the regionalisation of the developing vertebrate central nervous system. BioEssays 24:4270438
Pasman JW (1997) Auditory evoked responses in preterm infants. Thesis, University of Nijmegen
Pasqualetti M, Rijli FM (2001) Homeobox gene mutations and brain-stem developmental disorders: learning from knockout mice. Curr Opin Neurol 14:177–184
Pasqualetti M, Neun R, Devenne M, Rijli FM (2001) Retinoic acid rescues inner ear defects in Hoxa1 deficient mice. Nat Genet 29:34–39
Passos-Bueno MR, Ornelas CC, Fanganiello RD (2009) Syndromes of the first and second pharyngeal arches: a review. Am J Med Genet A 149A:1853–1859
Patel M, Hu BH (2012) MicroRNAs in inner ear biology and pathogenesis. Hear Res 287:6–14
Pattyn A, Morin X, Cremer H, Goridis C, Brunet J-F (1997) Expression and interactions of the two closely related homeobox genes Phox2a and Phox2b during neurogenesis. Development 124:4065–4075
Pattyn A, Morin X, Cremer H, Goridis C, Brunet J-F (1999) The homeobox gene Phox2b is essential for development of autonomic neural crest derivatives. Nature 399:366–370
Pattyn A, Goridis C, Brunet J-F (2000a) Specification of the central noradrenergic phenotype by the homeobox gene Phox2b. Mol Cell Neurosci 15:235–243
Pattyn A, Hirsch M-R, Goridis C, Brunet J-F (2000b) Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b. Development 127:1349–1358
Pattyn A, Vallstedt A, Dias JM, Sander M, Ericson J (2003) Complementary roles for Nkx6 and Nkx2 class proteins in the establishment of motoneuron identity in the hindbrain. Development 130:4149–4159
Pauley S, Wright TJ, Pirvola U, Ornitz D, Beisel K, Fritzsch B (2003) Expression and function of FGF10 in mammalian inner ear development. Dev Dyn 227:203–215
Pauley S, Lai E, Fritzsch B (2006) Foxg1 is required for morphogenesis and histogenesis of the mammalian inner ear. Dev Dyn 235:2470–2482
Pearson AA (1938) The spinal accessory nerve in human embryos. J Comp Neurol 68:243–266
Pearson AA (1939) The hypoglossal nerve in human embryos. J Comp Neurol 71:21–39
Pearson AA (1943) The trochlear nerve in human fetuses. J Comp Neurol 78:29–43
Pearson AA (1944) The oculomotor nucleus in the human fetus. J Comp Neurol 80:47–63
Pearson AA (1946) The development of the motor nuclei of the facial nerve in man. J Comp Neurol 85:461–476
Peck JE (1994) Development of hearing. Part II. Embryology. J Am Acad Audiol 5:359–365
Peck JE (1995) Development of hearing. Part III. Postnatal development. J Am Acad Audiol 6:113–123
Pedraza S, Gámez J, Rovira A, Zamora A, Grive E, Raguer N, Ruscolleda J (2000) MRI findings in Möbius syndrome: correlations with clinical features. Neurology 55:1058–1060
Pennings RJE (2004) Hereditary deaf-blindness. Clinical and genetic aspects. Thesis, University of Nijmegen
Pennings RJE, Huygen PLM, Van Camp G, Cremers CWRJ (2003) A review of progressive phenotypes in nonsyndromic autosomal dominant hearing impairment. Audiol Med 1:47–55
Peters LM, Anderson DW, Griffith AJ, Grundfast KM, San Agustin TB, Madeo AC et al (2002) Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28. Hum Mol Genet 11:2877–2885
Petit C, Levilliers J, Hardelin J-P (2001a) Molecular genetics of hearing loss. Annu Rev Genet 35:589–646
Petit C, Levilliers J, Marlin S, Hardelin J-P (2001b) Hereditary hearing loss. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic & molecular bases of inherited disease. McGraw-Hill, New York, pp 6281–6328
Phippard D, Lu L, Lee D, Saunders JC, Crenshaw EB (1999) Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear. J Neurosci 19:5980–5989
Pieh C, Lengyel D, Neff A, Fretz C, Gottlob I (2002) Brain stem hypoplasia in familial congenital horizontal gaze paralysis (FCGP) and kyphoscoliosis. Neurology 59:462–463
Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Preho MO, Puliti A et al (1998) SOX10 mutations in patients with Waardenburg-Hirschsprung disease. Nat Genet 18:171–173
Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N (2010) Review and update of mutations causing Waardenburg syndrome. Hum Mutat 31:391–406
Plantinga RF, Cremers CW, Huygen PL, Kunst HP, Bosman AJ (2007) Audiological evaluation of affected members from a Dutch DFNA8/12 (TECTA) family. J Assoc Res Otolaryngol 8:1–7
Poretti A, Boltshauser E, Plecko B (2007) Brainstem disconnection: case report and review of the literature. Neuropediatrics 38:210–212
Poretti A, Denecke J, Miller DC, Schiffmann H, Buhk JH, Grange DK et al (2015) Brainstem disconnection: two additional patients and expansion of the phenotype. Neuropediatrics 46:139–144
Price ER, Fisher DE (2001) Sensorineural deafness and pigmentation genes: melanocytes and the Mitf transcriptional network. Neuron 30:15–18
Proctor B, Nager GT (1982) The facial canal: normal anatomy, variations and anomalies. Ann Otol Rhinol Laryngol 91:33–61
Puelles L (1995) A segmental morphological paradigm for understanding vertebrate forebrains. Brain Behav Evol 46:319–337
Puelles L (2013) Plan of the vertebrate nervous system. Relating embryology to the adult nervous system (prosomere model, overview of brain organization). In: Rubenstein JLR, Rakic P (eds) Comprehensive developmental neuroscience, vol 1. Academic/Elsevier, Amsterdam, pp 187–209
Puelles L, Martínez S, Martínez de la Torre M (2008) Neuroanatomía. Edit Med Panamerícana, Buenos Aires, Madrid (in Spanish)
Puelles L, Tvrdik P, Martínez-de-la-Torre M (2019) The postmigratory alar topography of visceral cranial nerve efferents challenges the classical model of hindbrain columns. Anat Rec 302:485–504
Punal JE, Siebert MF, Angueira FB, Lorenzo AV, Castro-Gago M (2001) Three new patterns with congenital unilateral facial nerve palsy due to chromosome 22q11 deletion. J Child Neurol 16:450–452
Ramekers D, Versnel H, Grolman W, Klis SF (2012) Neurotrophins and their role in the cochlea. Hear Res 288:19–33
Ramirez J-M, Baertsch NA (2018) The dynamic basis of respiratory rhythm generation: one breath at a time. Annu Rev Neurosci 41:475–499
Read AP (2001) Waardenburg syndrome. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic & molecular bases of inherited disease. McGraw-Hill, New York, pp 6097–6116
Retzius G (1884) Das Gehörorgan der Wirbelthiere, vol II. Samson & Wallin, Stockholm
Reynolds JD, Biglan AW, Hiles DA (1984) Congenital superior oblique palsy in infants. Arch Ophthalmol 102:1503–1505
Rhinn M, Brand M (2001) The midbrain-hindbrain organizer. Curr Opin Neurobiol 11:34–42
Riazuddin S, Ahmad ZM, Fanning AS, Lagziel A, Kitajiri S et al (2006) Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet 79:1040–1051
Riazuddin S, Belyantseva IA, Giese APJ, Lee K, Indzhykulian AA, Nandamuri SP et al (2012) Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type Ij and nonsyndromic deafness DFNB48. Nat Genet 44:1265–1271
Riccomagno MM, Martinu L, Mulheisen M, Wu DK, Epstein DJ (2002) Specification of the mammalian cochlea is dependent on Sonic hedgehog. Genes Dev 16:2365–2378
Riccomagno MM, Takada S, Epstein DJ (2005) Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes Dev 19:1612–1623
Richardson GP, de Montel JB, Petit C (2011) How the genetics of deafness illuminates auditory physiology. Annu Rev Physiol 73:311–314
Riga M, Korres G, Chouridis P, Naxakis S, Danielidis V (2018) Congenital cytomegalovirus infection inducing non-congenital sensorineural hearing loss during childhood, a systematic review. Int J Pediatr Otorhinolaryngol 115:156–164
Rijli FM, Gavalas A, Chambon P (1998) Segmentation and specification in the branchial region of the head: the role of the Hox selector genes. Int J Dev Biol 42:393–401
Robiedo RF, Lufkin T (2006) Dlx5 and Dlx6 homeobox genes are required for specification of the mammalian vestibular apparatus. Genesis 44:425–437
Rosenberg ML (1984) Congenital trigeminal anesthesia, review and classification. Brain 107:1073–1082
Rossel M, Capecchi MR (1999) Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development 126:5027–5040
Rucker JC, Webb BD, Frempong T, Gaspar H, Naidich TP, Jabs EW (2014) Characterization of ocular motor deficits in congenital facial weakness: moebius and related syndromes. Brain 137:1068–1079
Rudnicki A, Avraham KB (2012) microRNAs: the art of silencing in the ear. EMBO Mol Med 4:849–859
Ruel J, Emery S, Nouvian R, Bersot T, Amilhon B, Van Rijbroek JM et al (2008) Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice. Am J Hum Genet 83:278–293
Sadl VS, Sing A, Mar L, Jin F, Cordes SP (2003) Analysis of hindbrain patterning defects caused by the kreislerneu mutation reveals multiple roles of Kreisler in hindbrain segmentation. Dev Dyn 227:134–142
Safieddine S, El-Amraoui A, Petit C (2012) The auditory hair cell ribbon synapse: from assembly to function. Annu Rev Neurosci 35:509–528
Saihan Z, Webster AR, Luxon L, Bitner-Glindzicz M (2009) Update on Usher syndrome. Curr Opin Neurol 22:19–27
Sambasivan R, Kuratani S, Tajbakhsh S (2011) An eye on the head: the development and evolution of craniofacial muscles. Development 138:2401–2415
Sandell L (2014) Neural crest cells in ear development. In: Trainor P (ed) Neural crest cells. Evolution, development and disease. Academic/Elsevier, San Diego, CA, pp 167–187
Sander M, Paydar S, Ericson J, Briscoe J, Berber E, German M, Jessell TM, Rubenstein JLR (2000) Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates. Genes Dev 14:2134–2139
Sando I, Wood RF (1971) Congenital middle ear anomalies. Otolaryngol Clin N Am 4:291–318
Sarnat HB (2004) Watershed infarcts in the fetal and neonatal brainstem. An aetiology of central hypoventilation, dysphagia, Möbius syndrome and micrognathia. Eur J Pediatr Neurol 8:71–87
Sarnat HB, Benjamin DR, Siebert JR, Kletter GB, Cheyette SR (2002) Agenesis of the mesencephalon and metencephalon with cerebellar hypoplasia: putative mutation in the EN2 gene—report of two cases in early infancy. Ped Dev Pathol 5:54–62
Satoh T, Fekete DM (2005) Clonal analysis of the relationships between mechanosensory cells and the neurons that innervate them in the chicken ear. Development 132:1687–1697
Saul SM, Brzezinski JA, Altschuler RA, Shore SE, Rudolph DD, Kabara LL et al (2008) Math5 expression and function in the central auditory system. Mol Cell Neurosci 37:153–169
Schimmang T (2013) Transcription factors that control inner ear development and their potential for transdifferentiation and reprogramming. Hear Res 297:84–90
Schneider-Maunoury S, Seitanidou T, Charnay P, Lumsden A (1997) Segmental and neuronal architecture of the hindbrain of Krox-20 mouse mutants. Development 124:1215–1226
Schuknecht HF (1993) Pathology of the ear. Lea & Febiger, Philadelphia, PA
Schuknecht HF, Churchill JA, Doran R (1959) The localization of acetylcholinesterase in the cochlea. Arch Otolaryngol 69:549–559
Schwarzacher SW, Rüb U, Deller T (2011) Neuroanatomical characteristics of the human pre-Bötzinger complex and its involvement in neurodegenerative brainstem diseases. Brain 134:24–35
Sennaroğlu L (2016) Histopathology of inner ear malformations: do we have enough evidence to explain pathophysiology? Cochlear Implants Int 17:13–20
Sennaroğlu L, Bajin MD (2017) Classification and current management of inner ear malformations. Balkan Med J 34:397–411
Sennaroğlu L, Saatci I (2002) A new classification for cochleovestibular malformations. Laryngoscope 112:2230–2241
Sennaroğlu L, Sara S, Ergin T (2006) Surgical results of cochlear implantation in malformed cochlea. Otol Neurotol 27:615–623
Severino M, Giraldo AF, Utz N, Tortora D, Pogledic I, Klonowski W et al (2020) Definitions and classification of malformations of cortical development: practical guidelines. Brain 143:2874–2894
Sharma K, Sheng HZ, Lettier K, Li H, Karavanov A, Potter S et al (1998) LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Cell 95:817–828
Shearer AE, Hansen MR (2019) Auditory synaptopathy, auditory neuropathy, and cochlear implantation. Laryngoscope Investig Otolaryngol 4:429–440
Sicotte NL, Salamon G, Shattuck DW, Hageman N, Rüb U, Salamon N et al (2006) Diffusion tensor MRI shows abnormal brainstem crossing fibers associated with ROBO3 mutations. Neurology 67:519–521
Siebenmann F, Bing R (1907) Über den Labyrinth- und Hirnbefund bei einem an Retinitis pigmentosa erblindeten angeborenen Taubstummen. Z Ohrenheilkd 54:265–280
Simmons D, Duncan J, de Caprona DC, Fritzsch B (2011) Development of the inner ear efferent system. In: Ryugo KD, Fay RR, Popper AN (eds) Auditory and vestibular efferents. Springer, New York, pp 187–218
Slepecky NB (1996) Structure of the mammalian cochlea. In: Dallos P, Popper AN, Fay RR (eds) The cochlea. Springer, New York, pp 44–129
Smithells R, Sheppard S, Holzel H, Jones G (1990) Congenital rubella in Great Britain 1971-1988. Health Trends 22:73–76
Smits JJ, Oostrik J, Beynor AJ, Kant SG, de Koning Gans PAM, Rotteveel LJC et al (2019) De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment. Hum Genet 138:61–72
Soldà G, Robusto M, Primignani P, Castorina P, Benzoni E, Cesarani A et al (2012) A novel mutation within the MIR96 gene causes non-syndromic hearing loss in an Italian family by altering pre-miRNA processing. Hum Mol Genet 21:577–580
Song JJ, Kwon JJ, Park MK, Seo YR (2013) Microarray analysis of microgene expression alteration in human middle ear epithelial cells induced by microparticles. Int J Pediatr Otorhinolaryngol 77:1760–1764
Song J, Feng Y, Acke FR, Coucke P, Vleminckx K, Dhooge IJ (2016) Hearing loss in Waardenburg syndrome: a systematic review. Clin Genet 89:416–425
Soukup GA, Fritzsch B, Pierce ML, Weston MD, Jahan I, McManus MT, Harfe BD (2009) Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice. Dev Biol 328:328–341
Spritz RA, Chiang P-W, Oiso N, Alkhateeb A (2003) Human and mouse disorders of pigmentation. Curr Opin Genet Dev 13:284–289
St. Charles S, Di Mario FJ Jr, Grunnet ML (1993) Möbius sequence: further in vivo support for the subclavian artery supply disruption sequence. Am J Med Genet 47:289–293
Steel KP, Barkway C (1989) Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear. Development 107:453–463
Steel KP, Kros CJ (2001) A genetic approach to understanding auditory function. Nat Genet 27:143–149
Stennert E, Arold R (1973) Der doppelte Gehörgang. Klinische Studie einer seltenen Missbildung mit besonderer Berücksichtigung der anatomischen Beziehung zum extratemporalen Facialisverlauf. HNO 21:293–296
Stone JS, Oesterle EC, Rubel EW (1998) Recent insights into regeneration of auditory and vestibular hair cells. Curr Opin Neurol 11:17–24
Storm R, Cholewa-Waclaw J, Reuter K, Brohl D, Sieber M, Treier M et al (2009) The bHLH transcription factor Olig3 marks the dorsal neuroepithelium of the hindbrain and is essential for the development of brainstem nuclei. Development 136:295–305
Stornetta RL (2008) Identification of neurotransmitters and co-localization of transmitters in brainstem respiratory neurons. Respir Physiol Neurobiol 164:18–27
Stornetta RL, Moreira TS, Takakura AC, Kang BJ, Chang DA, West GH et al (2006) Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat. J Neurosci 26:10305–10314
Streeter GL (1904) The development of the cranial and spinal nerves in the occipital region of the human embryo. Am J Anat 4:83–116
Streeter GL (1906) On the development of the membranous labyrinth and the acustic and facial nerves in the human embryo. Am J Anat 6:139–165
Streeter GL (1911) Die Entwicklung des Nervensystems. In: Keibel F, Mall FP (eds) Handbuch der Entwicklungsgeschichte des Menschen, Zweiter Band. Hirzel, Leipzig, pp 1–156
Streeter GL (1912) The development of the nervous system. In: Keibel F, Mall FP (eds) Manual of human embryology, vol 2. Lippincott, Philadelphia, PA, pp 1–156
Streeter GL (1918) The histogenesis and growth of the otic capsule and its contained periotic tissue-spaces in the human embryo. Contrib Embryol Carnegie Instn 7:5–54
Streeter GL (1922) Development of the auricle in the human embryo. Contrib Embryol Carnegie Instn 14:111–138
Streit A (2007) The preplacodal region: an ectodermal domain with multipotential progenitors that contribute to sense organs and cranial sensory ganglia. Int J Dev Biol 51:447–461
Studer M (2001) Initiation and growth of facial motoneurone migration is dependent on rhombomeres 5 and 6. Development 128:3707–3716
Studer M, Lumsden A, Ariza-McNaughton L, Bradley N, Krumlauf R (1996) Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1. Nature 384:630–634
Studer M, Gavalas A, Marshall H, Ariza-McNaughton L, Rijli FM, Chambon P, Krumlauf R (1998) Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning. Development 125:1025–1036
Sulik KK, Cotanche DA (2004) Embryology of the ear. In: Toriello HV, Reardon W, Gorlin RJ (eds) Hereditary hearing loss and its syndromes, 2nd edn. Oxford University Press, Oxford, pp 17–36
Szu J, Wojcinski A, Jiang P, Kesari S (2021) Impact of the Olig family on neurodevelopmental disorders. Front Neurosci 15:659601
Taber Pierce E (1967) Histogenesis of the dorsal and ventral cochlear nuclei in the mouse. An autoradiographic study. J Comp Neurol 131:27–54
Tassabehji M, Read AP, Newton VE, Harris R, Balling R, Gruss P, Strachan T (1992) Waardenburg’s syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature 355:635–636
Tassabehji M, Newton VE, Read AP (1994) Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. Nat Genet 8:251–255
TE2 (2017) Terminologia Embryologica, 2nd ed. FIPAT.library.dal.ca. Federative International Programme for Anatomical Terminology
ten Donkelaar HJ, Kaga K (2020) The auditory system. In: ten Donkelaar HJ (ed) Clinical neuroanatomy: brain circuitry and its disorders, 2nd edn. Springer, Cham, pp 373–407
ten Donkelaar HJ, Kachlik D, Tubbs RS (2018) An illustrated terminologia neuroanatomica. A concise encyclopedia of human neuroanatomy. Springer, Cham
ten Donkelaar HJ, Kachlik D, Cruysberg JRM, van der Vliet T, van Domburg P (2020a) The cranial nerves. In: ten Donkelaar HJ (ed) Clinical neuroanatomy: brain circuitry and its disorders, 2nd edn. Springer, Cham, pp 309–372
ten Donkelaar HJ, Němcova V, Lammens M, Overeem S (2020b) The autonomic nervous system. In: ten Donkelaar HJ (ed) Clinical neuroanatomy: brain circuitry and its disorders, 2nd edn. Springer, Cham, pp 669–710
ten Donkelaar HJ, Elliott KL, Fritzsch B, Kachlik D, Carlson M, Isaacson B et al (2020c) An updated terminology for the internal ear with combined anatomical and clinical terms. J Phonet Audiol 6:147
Teunissen E (1992) Major and Minor Congenital Anomalies of the Ear. Classification and surgical results. Thesis, University of Nijmegen
Tewfik TL, Der Kaloustian VM (eds) (1997) Congenital anomalies of the ear, nose, and throat. Oxford University Press, New York
Thakkar N, O’Neil W, Duvally J, Liu C, Ambler M (1977) Möbius syndrome due to brain stem tegmental necrosis. Arch Neurol 34:124–126
Thompson H, Tucker AS (2013) Dual origin of the epithelium of the mammalian middle ear. Science 339:1453–1456
Thompson H, Ohazama A, Sharpe PT, Tucker AS (2012) The origin of the stapes and relationship to the otic capsule and oval window. Dev Dyn 241:1396–1404
Tischfield MA, Bosley TM, Salih MA, Alorainy IA, Sener EC, Nester MJ et al (2005) Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovacular and cognitive development. Nat Genet 37:1035–1037
Tischfield MA, Baris HN, Wu C, Rudolph G, Van Maldergem L, He W et al (2010) Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 140:74–87
TNA (2017) Terminologia Neuroanatomica. FIPAT.library.dal.ca. Federative International Programme for Anatomical Terminology
Tomás-Roca L, Corral-San-Miguel R, Aroca P, Puelles L, Marín F (2016) Crypto-rhombomeres of the mouse medulla oblongata, defined by molecular and morphological features. Brain Struct Funct 221:815–838
Toms M, Pagarkar W, Moosajee M (2020) Usher syndrome: clinical features, molecular genetics and advancing therapeutics. Ther Adv Ophthalmol 12:2515841420952194
Topsakal V, Kachlik D, Bahşi I, Carlson M, Isaacson B, Broman J et al (2021) Relevant temporal bone anatomy for robotic cochlear implantation: an updated terminology combined with anatomical and clinical terms. Translat Res Anat 25:100138
Toriello HV, Smith SD (eds) (2013) Hereditary hearing loss and its syndromes, 3rd edn. Oxford University Press, New York
Toriello HV, Reardon W, Gorlin RJ (eds) (2004) Hereditary hearing loss and its syndromes, 2nd edn. Oxford University Press, Oxford, New York
Tos M (2000) Surgical solutions for conductive hearing loss. Thieme, Stuttgart
Towfighi J, Marcks K, Palmer E, Vannucci R (1979) Möbius syndrome. Neuropathologic observations. Acta Neuropathol (Berl) 48:11–17
Trainor PA, Krumlauf R (2000) Patterning the cranial neural crest: hindbrain segmentation and Hox gene plasticity. Nat Rev Neurosci 1:116–124
Tranebjaerg L, Samson RA, Greene GE (2012) Jervell and Lange-Nielsen syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP (eds) Gene reviews (Internet). University of Washington, Seattle, WA
Tsuchida T, Ensini M, Morton SB, Baldassare M, Edlund T, Jessell TM, Pfaff SL (1994) Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes. Cell 79:957–970
Urbanek P, Wang ZQ, Fetka L, Wagner EF, Busslinger M (1994) Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell 79:901–912
Urness LD, Paxton CN, Wang X, Schoenwolf GC, Mansour SL (2010) FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a. Dev Biol 340:595–604
Usami S, Abe S, Weston MD, Shinkawa H, Van Camp G, Kimberling WJ (1999) Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations. Hum Genet 104:188–192
Usher CH (1914) On the inheritance of retinitis pigmentosa, with notes of a case. R Lond Ophthalmol Hosp Rep 19:130–236
Vaage S (1969) The segmentation of the primitive neural tube in chick embryos (Gallus domesticus). Ergebn Anat Entw Gesch 41:1–88
Vahava O, Morell R, Lynch ED, Weiss S, Kagan ME, Ahituv N et al (1998) Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans. Science 279:1950–1954
van Aarem A, Cremers CWRJ, Benraad-van Rens MJL (1995) The Usher syndrome: a temporal bone report. Arch Otolaryngol Head Neck Surg 121:916–921
van Beeck Calkoen EA, Merkus P, Goverts ST, van de Kamp JM, Mulder MF, Sanchez Aliaga E, Hensen EF (2018) Evaluation of the outcome of CT and MR imaging in pediatric patients with bilateral sensorineural hearing loss. Int J Pediatr Otorhinolaryngol 108:180–185
van Beeck Calkoen EA, Engel MSD, van de Kamp JM, Yntema HG, Goverts ST, Mulder MF et al (2019) The etiological evaluation of sensorineural hearing loss in children. Eur J Pediatr 178:1195–1205
Van De Water TR, Noden DM, Maderson PFA (1988) Embryology of the ear: outer, middle and inner. Otol Med Surg 1:3–27
van den Munckhof P, Luk KC, Ste-Marie L, Montgomery J, Blanchet PJ, Sadikot AF, Drouin J (2003) Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons. Development 130:2535–2542
van der Heijden ME, Zoghbi HY (2020) Development of the brainstem respiratory circuit. WIREs Dev Biol 9:e366
van Wijk E, Krieger E, Kemperman MH, De Leenheer EM, Huygen PL, Cremers CW et al (2003) A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26). J Med Genet 40:879–884
Varela-Echeverria A, Pfaff SL, Guthrie S (1996) Differential expression of LIM homeobox genes among motor neuron populations in the developing chick brain stem. Mol Cell Neurosci 8:242–257
Velde HM, Reurink J, Held S, Li CHZ, Yzer S, Oostrik J et al (2022) Usher syndrome type IV. Clinically and molecularly confirmed by novel ARSG variants. Hum Genet 141(11):1723–1738
Verhoeven K, Van Laer L, Kirschhofer K, Legan PK, Hughes DC, Schatteman I et al (1998) Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment. Nat Genet 19:60–62
Verzijl HTFM, van den Helm B, Veldman B, Hamel BCJ, Kuyt LP, Padberg GW, Kremer H (1999) A second gene for autosomal dominant Möbius syndrome is localized to chromosome 10q in a Dutch family. Am J Hum Genet 65:752–756
Verzijl HTFM, van der Zwaag B, Cruysberg JRM, Padberg GW (2003) Möbius syndrome redefined. A syndrome of rhombencephalic maldevelopment. Neurology 61:327–333
Verzijl HTFM, van der Zwaag B, Lammens M, ten Donkelaar HJ, Padberg GW (2005) The neuropathology of hereditary congenital facial palsy versus Möbius syndrome. Neurology 64:649–653
Vesseur AC, Verbist BM, Westerlaan HE, Kloostra FJJ, Admiraal RJC, van Ravenswaaij-Arts CMA et al (2016) CT findings of the temporal bone in CHARGE syndrome: aspects of importance in cochlear implant surgery. Ur Arch Otorhinolaryngol 273:4225–4240
Victor DI (1976) The diagnosis of congenital third-nerve palsy. Brain 99:711–718
Vieille-Grosjean I, Hunt P, Gulisano M, Boncinelli E, Thorogood P (1997) Branchial HOX gene expression and human craniofacial development. Dev Biol 183:49–60
Vikkula M, Mariman EC, Lui VC, Zhidhova NI, Tiller GE, Goldring MB et al (1995) Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus. Cell 80:431–437
Vollrath MA, Kwan KY, Corey DP (2007) The micromachinery of mechanotransduction in hair cells. Annu Rev Neurosci 30:339–365
von Graefe A (1858) Vereinzelte Beobachtungen exceptionelles Verhalten des Gesichtsfeldes bei Pigmententartung der Netzhaut. Albrecht von Graefe’s Arch Klin Ophthalmol 4:250–253
von Graefe A (1880) In: von Graefe A, Saemisch T (eds) Handbuch der gesamten Augenheilkunde, vol 6. Engelmann, Leipzig, p 60
Von Noorden GK, Murray E, Wong SY (1986) Superior oblique paralysis: a review of 270 cases. Arch Ophthalmol 104:1771–1776
Waardenburg PJ (1951) A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet 3:195–253
Wagenaar M, Draaijer P, Meek H, ten Donkelaar HJ, Wesseling P, Kimberling W, Cremers C (1999) The cochlear nuclei in two patients with Usher syndrome type I. Int J Pediatr Otolaryngol 50:185–195
Wagenaar M, Schuknecht H, Nadol J Jr, Benraad-van Rens MJL, Kimberling WJ, Cremers CWRJ (2000) Histopathology of the temporal bone in Usher syndrome type I. Arch Otolaryngol Head Neck Surg 126:1018–1023
Wallis D, Hamblen M, Zhou Y, Venken KJT, Schumacher A, Leighton Grimes H et al (2003) The zinc finger transcription factor Gfi1, implicated in lymphogenesis, is required for inner ear hair cell differentiation and survival. Development 130:221–232
Walsh T, Pierce SB, Lenz DR, Brownstein Z, Dagan-Rosenfeld O, Shahin H et al (2010) Genomic duplication and overexpression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51. Am J Hum Genet 87:101–109
Wan G, Corfas G, Stone JS (2013) Inner ear supporting cells: rethinking the silent majority. Semin Cell Dev Biol Epub:S1084–S9521
Wang S, Zwaan J, Mullaney P, Jabok MH, Al-Awad A, Beggs AH, Engle EC (1998) Congenital fibrosis of the extraocular muscles type 2 (CFEOM2), an inherited exotropic strabismus fixus, maps to distal 11q13. Am J Hum Genet 63:517–525
Wang W, Chan EK, Baron S, Van De Water T, Lufkin T (2001) Hmx2 homeobox gene control of murine vestibular morphogenesis. Development 128:5017–5029
Wangemann P (2002) K+ cycling and its regulation in the cochlea and the vestibular labyrinth. Audiol Neurootol 7:199–205
Wangemann P (2011) The role of pendrin in the development of the murine inner ear. Cell Physiol Biochem 28:527–534
Wassef M, Joyner AL (1997) Early mesencephalon/metencephalon patterning and development of the cerebellum. Persp Dev Neurobiol 5:3–16
Watson C (2012) Hindbrain. In: Watson C, Paxinos G, Puelles L (eds) The mouse nervous system. Elsevier, Amsterdam, pp 398–423
Watson C, Shimogori T, Puelles L (2017) Mouse Fgf8-Cre-LacZ lineage defines the territory of the postnatal mammalian isthmus. J Comp Neurol 525:2782–2799
Wayne S, Robertson NG, De Clau F, Chen N, Verhoeven K, Prased S et al (2001) Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum Mol Genet 10:195–200
Webb BD, Shaaban S, Gaspar H, Cunha LF, Schubert CZ, Hao K et al (2012) HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1−/− mice. Am J Hum Genet 91:171–179
Weerda H (2004) Verletzungen, Defekte und Anomalien. In: Weerda H (ed) Chirurgie der Ohrmuschel. Thieme, Stuttgart, pp 105–226, 253–256
Weese-Mayer DE, Berry-Kravis EM, Zhou L, Maher BS, Silvestri JM, Curran ME, Marazita ML (2003) Idiopathic congenital central hypoventilation syndrome: analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2B. Am J Med Genet 123A:267–279
Wesdorp M, de Koning Gans PAM, Schraders M, Oostrik J, Huynen MA, Wenselaar H et al (2018) Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction. Hum Genet 137:389–400
Whitman MC (2021) Axonal growth anomalies underlying ocular cranial nerve disorders. Annu Rev Vision Sci 7:827–850
Whitman MC, Engle EC (2017) Ocular congenital dysinnervation disorders (CCDDs): insights into axon growth and guidance. Hum Mol Genet 26:R37–R44
Whitman MC, Engle EC (2022a) Congenital fibrosis of the extraocular muscles. In: Black GCM, Ashworth JL, Sergouniotis PI (eds) Clinical ophthalmic genetics and genomics. Academic Press, London, pp 408–411
Whitman MC, Engle EC (2022b) Moebius syndrome. In: Black GCM, Ashworth JL, Sergouniotis PI (eds) Clinical ophthalmic genetics and genomics. Academic Press, London, pp 422–424
Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E et al (2005) MicroRNA expression in zebrafish embryonic development. Science 309:310–311
Wilcox ER, Burton QL, Naiz S, Riazuddin S, Smith TN, Ploplis B et al (2001) Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Cell 104:165–172
Wilkinson DG, Bhatt S, Cook M, Boncinelli E, Krumlauf R (1989) Segmental expression of Hox-2 homeobox-containing genes in the developing mouse hindbrain. Nature 341:405–409
Willard FH, Martin GF (1986) The development and migration of large multipolar neurons into the cochlear nucleus of the North American opossum. J Comp Neurol 248:119–132
Willinger M, James LS, Catz C (1991) Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development. Pediatr Pathol 11:677–684
Wineland A, Menezes MD, Shimony JS, Shinawi MS, Hullar TH, Hirose K (2017) Prevalence of semicircular canal hypoplasia in patients with CHARGE syndrome: 3C syndrome. JAMA Otolaryngol Head Neck Surg 143:168–177
Wurst W, Bally-Cuif L (2001) Neural plate patterning: upstream and downstream of the isthmic organizer. Nat Rev Neurosci 2:99–108
Wurst W, Auerbach AB, Joyner AL (1994) Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development 120:2065–2075
Xu PX, Adams J, Peters H, Brown MC, Heaney S, Maas R (1999) Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet 23:113–117
Xu J, Li J, Zhang T, Jiang H, Ramakrishnan A, Fritzsch B (2021) Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm. Proc Natl Acad Sci U S A 118:e2025196118
Yamada K, Andrews C, Chan WM et al (2003) Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Nat Genet 35:318–321
Yamada M, Terao M, Terashima T, Fujiyama T, Kawaguchi Y, Nabeshima Y, Hoshino M (2007) Origin of cimbing fiber neurons and their developmental dependence on Ptf1a. J Neurosci 27:10924–10934
Yang T, Kersigo J, Jahan I, Pan N, Fritzsch B (2011) The molecular basis of making spiral ganglion neurons and connecting them to hair cells of the organ of Corti. Hear Res 278:21–33
Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N et al (1999) A mutation in OTOF, encoding otoferlin, causes DFNB9, a nonsyndromic form of deafness. Nat Genet 21:363–369
Yildirim R, Arslanoğlu A, Mahiroğullari M, Sahan M, Ozkan H (2008) Klippel-Feil syndrome and associated ear anomalies. Am J Otolaryngol 29:319–325
Zaki MC, Saleem SN, Dobyns WB, Barkovich AJ, Bartsch H, Dale AM et al (2012) Diencephalic-mesencephalic junction dysplasia: a novel recessive brain malformation. Brain 135:2416–2427
Zec N, Filiano JJ, Kinney HC (1997) Anatomic relationships of the human arcuate nucleus of the medulla: a DiI-labeling study. J Neuropathol Exp Neurol 56:509–522
Zhao HB, Kikuchi T, Ngezahayo A, White TW (2006) Gap junctions and cochlear homeostasis. J Membr Biol 209:177–186
Zheng W, Huang L, Wei Z-B, Silvius D, Tang B, Xu P-X (2003) The role of Six1 in mammalian auditory system development. Development 130:3989–4000
Zhou Q, Anderson DJ (2002) The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 109:61–73
Zhu M, Yang T, Wei S, DeWan AT, Morell RJ, Elfenbein JL et al (2003) Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26). Am J Hum Genet 73:1082–1091
Zou D, Erickson C, Kim E, Jin D, Fritzsch B, Xu PX (2008) Eya1 gene dosage critically affects the development of sensory epithelia in the mammalian inner ear. Hum Mol Genet 17:3340–3356
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ten Donkelaar, H.J., Fritzsch, B., Cruysberg, J.R.M., Pennings, R.J.E., Smits, J.J., Lammens, M. (2023). Development and Developmental Disorders of the Brain Stem. In: Clinical Neuroembryology. Springer, Cham. https://doi.org/10.1007/978-3-031-26098-8_7
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