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Role of Shh in the development of molecularly characterized tegmental nuclei in mouse rhombomere 1

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Abstract

Hindbrain rhombomeres in general are differentially specified molecularly by unique combinations of Hox genes with other developmental genes. Rhombomere 1 displays special features, including absence of Hox gene expression. It lies within the hindbrain range of the Engrailed genes (En1, En2), controlled by the isthmic organizer via diffusion of FGF8. It is limited rostrally by the isthmus territory, and caudally by rhombomere 2. It is double the normal size of any other rhombomere. Its dorsal part generates the cerebellar hemispheres and its ventral part gives rise to several populations, such as some raphe nuclei, the interpeduncular nucleus, the rhabdoid nucleus, anterior, dorsal, ventral and posterodorsal tegmental nuclei, the cholinergic pedunculopontine and laterodorsal tegmental nuclei, rostral parts of the hindbrain reticular formation, the locus coeruleus, and part of the lateral lemniscal and paralemniscal nuclei, among other formations. Some of these populations migrate tangentially before reaching their final positions. The morphogen Sonic Hedgehog (Shh) is normally released from the local floor plate and underlying notochord. In the present report we explore, first, whether Shh is required in the specification of these r1 populations, and, second, its possible role in the guidance of tangentially migrating neurons that approach the midline. Our results indicate that when Shh function is altered selectively in a conditional mutant mouse strain, most populations normally generated in the medial basal plate of r1 are completely absent. Moreover, the relocation of some neurons that normally originate in the alar plate and migrate tangentially into the medial basal plate is variously altered. In contrast, neurons that migrate radially (or first tangentially and then radially) into the lateral basal plate were not significantly affected.

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Abbreviations

ATg:

Anterior tegmental nucleus

CA:

Caudal apical interpeduncular subnucleus

Cb:

Cerebellum

cDR:

Caudal dorsal raphe nucleus

Ch:

Choroid tela

CLi:

Caudal linear nucleus

DLL:

Dorsal nucleus of the lateral lemniscus

DR:

Dorsal raphe

DTg:

Dorsal tegmental nucleus

gV:

Trigeminal ganglion

III:

Oculomotor nucleus

IF:

Interfascicular nucleus

Inc:

Nucleus incertus

ILL:

Intermediate nucleus of the lateral leminscus

IOC:

Inferior olive complex

IP:

Interpeduncular nucleus

IPC:

Caudal part of the interpeduncular nucleus

IPL:

Intermediate paralemniscal nucleus

IPR:

Rostral part of the interpeduncular nucleus

Is:

Isthmus

isDR:

Isthmic dorsal raphe nucleus

IV:

Trochlear nucleus

IV ventr:

Fourth ventricle

LC:

Locus coeruleus

LDTg:

Laterodorsal tegmental nucleus

m (1–2):

Mesomere (1–2)

Mes:

Mesencephalon

MesV:

Mesencephalic trigeminal nucleus

MnR:

Median raphe nucleus

p (1–3):

Prosomere (1–3)

PAG:

Periaqueductal gray

PB:

Parabrachial nucleus

PDTg:

Posterodorsal tegmental nucleus

PPnR:

Prepontine raphe nucleus

PPTg:

Pedunculopontine tegmental nucleus

Pro:

Prodromal nucleus

r (1–11):

Rhombomeres (1–11)

r1SuLR:

Rhombomere 1 supralemniscal raphe complex

RA:

Rostral apical interpeduncular subnucleus

Rbd:

Rhabdoid nucleus

Ret:

Reticular formation

Rf:

Raphe formation

Rhomb:

Rhombencephalon

RN:

Red nucleus

SNc:

Substantia nigra compacta

sc:

Spinal cord

Sph:

Sphenoid nucleus

SVe:

Sensitive vestibular complex

Svp:

Principal sensitive trigeminal nucleus

v:

Ventricle

V:

Trigeminal nucleus

VI:

Abducens nucleus

VII:

Facial nucleus

VLL:

Ventral nucleus of the lateral leminscus

Vm:

Trigeminal motor nucleus

VTg:

Ventral tegmental nucleus

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Acknowledgments

Work supported by “Ministerio de Economía y Competitividad” BFU2010-16548 (FEDER Fonds) to E. Puelles, Consolider Grant (CSD2007-00023) and European commission (EUCOMMTOOLS, contract 261492) to S.M., and “Ministerio de Economía y Competitividad” grant BFU2008-01456 and Fundación SENECA contract 04548/GERM/06 (no. 10891) to L. Puelles. J.A. Moreno-Bravo was supported by the Predoctoral Program of the “Consejo Superior de Investigaciones Científicas-Junta de Ampliación de Estudios”, co-financed by the European Social Fund.

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Authors and Affiliations

  1. Instituto de Neurociencias, UMH-CSIC, Campus de San Juan, Av. Ramón y Cajal S/N, Sant Joan d’Alacant, 03550, Alicante, Spain

    J. A. Moreno-Bravo, A. Perez-Balaguer, J. E. Martinez-Lopez, S. Martinez & E. Puelles

  2. Departamento de Anatomía Humana y Psicobiología, Facultad de Medicina, Universidad de Murcia, Campus de Espinardo, 30100, Murcia, Spain

    P. Aroca & L. Puelles

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  1. J. A. Moreno-Bravo
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  2. A. Perez-Balaguer
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  3. J. E. Martinez-Lopez
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  4. P. Aroca
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  5. L. Puelles
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  6. S. Martinez
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Correspondence to E. Puelles.

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429_2013_534_MOESM1_ESM.tif

ESM 1. In the absence of Shh function, an Otx2 -positive population targets the IPC, and an Otp -positive population targets the IPR. a, b, e, f, Transversal sections to r1 of wild-type (a, e) and mutant mouse (b, f) E14.5 embryos stained with in situ hybridization for Otx2 (a, b) and Otp (e, f), or immunoreacted against PAX7 (a, b). c, d, g, h, sagittal sections of wild-type (c, g) and mutant (d, h) E18.5 embryos stained with in situ hybridization for Otx2 (c, d) and Otp (g, h). The basal Otx2-positive migration restricted to the caudal rhombomere1 is still present in the conditional mutant (arrow in b, d) but displays distinct reduction. The Otp-positive tangential migration into the IP complex was also detected at the rostral r1 (f, h). However, these cells do not colonize properly the IPR. The dotted line in c, d indicates the plane of section in a, b, e, f. Scale bar 200 μm. (TIFF 9946 kb)

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Moreno-Bravo, J.A., Perez-Balaguer, A., Martinez-Lopez, J.E. et al. Role of Shh in the development of molecularly characterized tegmental nuclei in mouse rhombomere 1. Brain Struct Funct 219, 777–792 (2014). https://doi.org/10.1007/s00429-013-0534-6

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