Abstract
In the developing mouse hindbrain, immunoreactivity for calretinin, a calcium-binding protein, was first observed at embryonic day 10, and was localized to neuronal cell bodies in the reticular formation. By embryonic day 12, fibers emanated rostrally from the calretinin-immunoreactive neurons, extended dorsally and then caudally in the uncinate fasciculus to reach the developing cerebellar plate. These fibers crossed the cerebellar midline and were distributed to the contralateral side of the cerebellum. The number and intensity of staining of cell bodies in the reticular formation was reduced in postnatal mice. After postnatal day 1, it was no longer possible to discern the calretinin-immunoreactive fiber bundle in the brainstem, although fibers were still visible at the level of the uncinate fasciculus and in the cerebellum. We also observed intensely calretinin-immunoreactive, smaller cells in the cerebellum (embryonic day 14) and dorsal cochlear nuclei (embryonic day 18), most of which we believe are destined to become the “unipolar brush”, (also known as “pale” or “monodendritic”) cells observed in the adult mammalian brain. An immature form of these cells exists in the developing mouse cerebellum. Thus, using calretinin antiserum as a marker, an afferent neuronal system was described which projects to the cerebellar primordium. It is suggested that the calretinin-containing hook bundle is an afferent projection which provides a feed-forward neuronal system to the cerebellum which, in turn, projects afferent fibers to the calretinin-containing and other cells of the reticular formation.
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References
Achenbach KE, Goodman DC (1968) Cerebellar projections to pons, medulla and spinal cord in the albino rat. Brain Behav Biol 1:43–57
Altman J (1972) Postnatal development of the cerebellar cortex in the rat. II. Phases in the maturation of Purkinje cells and molecular layer. J Comp Neurol 145:399–464
Altman J, Bayer SA (1977) Time of origin and distribution of a new cell type in the rat cerebellar cortex. Exp Brain Res 29:265–274
Altman J, Bayer SA (1978) Prenatal development of the cerebellar system of the rat. I. Cytogenesis and histogenesis of the deep nuclei and the cortex of the cerebellum. J Comp Neurol 179:23–48
Altman J, Bayer SA (1985a) Embryonic development of the rat cerebellum. I. Delineation of the cerebellar primordium and early cell movements. J Comp Neurol 231:1–26
Altman J, Bayer SA (1985b) Embryonic development of the rat cerebellum. II. Translocation and regional distribution of the deep neurons. J Comp Neurol 231:27–41
Altman J, Bayer SA (1985c) Embryonic development of the rat cerebellum. III. Regional differences in the time of origin, migration and settling of Purkinje cells. J Comp Neurol 231:42–65
Andressen C, Blümcke I, Celio MR (1993) Calcium-binding proteins: selective markers of nerve cells. Cell Tissue Res 271:181–208
Angaut P, Bowsher D (1970) Ascending projections of the medial cerebellar (fastigial) nucleus: an experimental study in the cat. Brain Res 24:49–68
Arai R, Winsky L, Arai M, Jacobowitz DM (1991) Immunohisto-chemical localization of calretinin in the rat hindbrain. J Comp Neurol 310:21–44
Baimbridge KG, Celio MR, Rogers JH (1992) Calcium-binding proteins in the nervous system. Trends Neurosci 15:303–308
Bastianelli E, Pochet R (1993) Transient expression of calretinin during development of chick cerebellum. Comparison with calbindin-D28k. Neurosci Res 17:53–61
Berthié B, Axelrad H (1994) Granular layer collaterals of the unipolar brush cell axon display rosette-like excrescences. A Golgi study in the rat cerebellar cortex. Neurosci Let 167:161–165
Bishop GA, Ho RH (1985) The distribution and origin of serotonin immunoreactivity in the rat cerebellum. Brain Res 331:195–207
Björklund A, Hökfelt T, Tohyama M (eds) (1992) Handbook of chemical neuroanatomy, vol 10. Ontogeny of transmitters and peptides in the CNS. Elsevier, Amsterdam, pp 1–663
Braak E, Braak H (1993) The new monodendritic neuronal type within the adult human cerebellar granule cell layer shows calretinin-immunoreactivity. Neurosci Lett 154:199–202
Carpenter MB, Brittin GM, Pines J (1958) Isolated lesions of the fastigial nuclei in the cat. J Comp Neurol 109:65–90
Celio MR (1990) Calbindin D-28k and parvalbumin in the rat nervous system. Neuroscience 35:375–475
Cozzi MG, Rosa P, Greco A, Hille A, Huttner WB, Zanini A, De Camilli P (1989) Immunohistochemical localization of secret-ogranin II in the rat cerebellum. Neuroscience 28:423–441
Dahlström A (1971) Axoplasmic transport (with particular respect to adrenergic neurons). Philos Trans R Soc Lond Biol 261:325–358
Ellis JH, Richards DE, Rogers JH (1991) Calretinin and calbindin in the retina of the developing chick. Cell Tissue Res 264:197–208
Enderlin S, Norman AW, Celio MR (1987) Ontogeny of the calcium-binding protein calbindin D-28k in the rat nervous system. Anat Embryol 177:15–28
Faull RLM (1978) The cerebellofugal projections in the brachium conjunctivum of the rat. J Comp Neurol 178:519–536
Floris A, Dino M, Jacobowitz DM, Mugnaini E (1994) The unipolar brush cells of the rat cerebellar cortex are calretinin positive: a study by light and electron microscopic immunocyto-chemistry. Anat Embryol 189:495–520
Harris J, Moreno S, Shaw G, Mugnaini E (1993) Unusual neurofilament composition in cerebellar unipolar brush neurons. J Neurocytol 22:1039–1059
Hockfield S (1987) A mab to a unique cerebellar neuron generated by immuno-suppression and rapid immunization. Science 237:67–70
Iacopino AM, Rhoten WB, Christakos S (1990) Calcium-binding protein (calbindin-D28K) gene expression in the developing and aging mouse cerebellum. Mol Brain Res 8:283–290
Jacobowitz DM, Winsky L (1991) Immunocytochemical localization of calretinin in the forebrain of the rat. J Comp Neurol 304:198–218
Kerr CWH, Bishop GA (1991) Topographical organization of the origin of serotonergic projections to different regions of the cat cerebellar cortex. J Comp Neurol 304:502–515
Korneliussen HK (1968) On the ontogenetic development of the cerebellum (nuclei, fissures, and cortex) of the rat, with special reference to regional variations in corticogenesis. J Hirnforsch 10:379–412
Laxson LC, King JS (1983) The formation and growth of the cortical layers of the cerebellum of the opossum. Anat Embryol 167:391–409
Legrand C, Thomasset M, Parkes CO, Clavel MC, Rabie A (1983) Calcium-binding protein in the developing rat cerebellum. Cell Tissue Res 233:389–402
Martin GF, Cabana T, Waltzer R (1988) The origin of projections from the medullary reticular formation to the spinal cord, the diencephalon and the cerebellum at different stages of development in the North American opossum: studies using single and double labeling techniques. Neuroscience 25:87–96
Mattson MP, Rychlik B, Chu D, Christakos S (1991) Evidence for calcium-reducing and calcium-binding protein calbindin-D28K in cultured hippocampal neurons. Neuron 6:41–51
Meiler K, Glees P (1969) The development of the mouse cerebellum. A Golgi and electron microscopic study. In: Llinas R (ed) Neurobiology of cerebellar evolution and development. AMA-ERF Press, Chicago, pp 783–801
Miale IL, Sidman RL (1961) An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp Neurol 4:277–296
Mugnaini E, Floris A (1994) The unipolar brush cell: a neglected neuron of the mammalian cerebellar cortex. J Comp Neurol 339:174–180
Munoz DG (1990) Monodendritic neurons: a cell type in the human cerebellar cortex identified by chromogranin A-like immunoreactivity. Brain Res 528:335–338
Mussen AT (1927) Experimental investigations on the cerebellum. Brain 50:313–349
Palkovits M, Jacobowitz DM (1974) Topographic atlas of catecholamine and acetylcholinesterase-containing neurons in the brain. II. Hindbrain (mesencephalon, rhombencephalon). J Comp Neurol 157:29–41
Parmentier M (1990) The human calbindins: cDNAs and gene cloning. Adv Exp Med Biol 255:233–240
Ramon y Cajal S (1960) Studies on vertebrate neurogenesis. Thomas, Springfield, Illinois, pp 302–317
Rasmussen AT (1933) Origin and course of the fasciculus uncinatus (Russell) in the cat, with observations on other fiber tracts arising from the cerebellar nuclei. J Comp Neurol 57:165–197
Résibois A, Rogers JH (1992) Calretinin in the rat brain: an immunohistochemical study. Neuroscience 46:101–134
Rogers JH (1989) Immunoreactivity for calretinin and other calcium-binding proteins in cerebellum. Neuroscience 31:711–721
Russell JSR (1897) The origin and destination of certain afferent and efferent tracts in the medulla oblongata. Brain 20:409–440
Schambra UB, Lauder JM, Silver J (1992) Atlas of the prenatal mouse brain. Academic Press, San Diego
Shi A-R, Itzkowitz SH, Kim YS (1988) A comparison of three immunoperoxidase techniques for antigen detection in colorectal carcinoma tissues. J Histochem Cytochem 36:317–322
Solbach S, Celio MR (1991) Ontogeny of the calcium-binding protein parvalbumin in the rat nervous system. Anat Embryol 184:103–124
Strauss KI, Jacobowitz DM (1993) Quantitative measurement of calretinin and β-actin mRNA in rat brain micropunches without prior isolation of RNA. Mol Brain Res 20:229–239
Sturrock RR (1990) A quantitative histological study of Golgi II neurons and pale cells in different cerebellar regions of the adult and ageing mouse brain. Z Mikrosk Anat Forsch 104:705–714
Taber Pierce E (1975) Histogenesis of the deep cerebellar nuclei in the mouse: an autoradiographic study. Brain Res 95:503–518
Thomas DM, Kaufman RP, Sprague JM, Chambers WW (1956) Experimental studies of the vermal cerebellar projections in the brain stem of the cat (fastigiobulbar tract). J Anat 90:371–385
Waltzer R, Martin GF (1984) Collateralization of reticulospinal axons from the nucleus reticularis gigantocellularis to the cerebellum and diencephalon. A double-labelling study in the rat. Brain Res 293:153–158
Winsky L, Jacobowitz DM (1991) Purification, identification and regional localization of a brain-specific calretinin-like calcium-binding protein (Protein 10) In: Heitzmann C (ed) Novel calcium-binding proteins — fundamentals and clinical implications. Springer, Heidelberg Berlin New York, pp 277–300
Winsky L, Nakata H, Martin BM, Jacobowitz DM (1989) Isolation, partial amino acid sequence, and immunocytochemical localization of a brain-specific calcium-binding protein. Proc Natl Acad Sci USA 86:10139–10143
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Abbott, L.C., Jacobowitz, D.M. Development of calretinin-immunoreactive unipolar brush-like cells and an afferent pathway to the embryonic and early postnatal mouse cerebellum. Anat Embryol 191, 541–559 (1995). https://doi.org/10.1007/BF00186743
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DOI: https://doi.org/10.1007/BF00186743