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First published online 9 February 2005
doi: 10.1242/dev.01683
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1 EPHE Quantitative Cell Biology, INSERM EMI 343, IFR 122, University
Montpellier 2, 34090 Montpellier, France
2 Laboratoire de Neurobiologie Cellulaire et Moléculaire, UPR 9040 CNRS,
1 Avenue de la Terrasse, 91198 Gif sur Yvette, France
3 INSERM UMR 623, IBDM Campus de Luminy, Case 907, 13288 Marseille Cedex 09,
France
4 INSERM U.583 Institut des Neurosciences de Montpellier (INM), Hôpital St
ELOI, 80 rue Augustin Fliche, 34295 Montpellier Cedex 5, France
* Author for correspondence (e-mail: mrossel{at}univ-montp2.fr)
Accepted 5 January 2005
The cytoarchitecture of the hindbrain results from precise and co-ordinated sequences of neuronal migrations. Here, we show that reelin, an extracellular matrix protein involved in neuronal migration during CNS development, is necessary for an early, specific step in the migration of several hindbrain nuclei. We identified two cell populations not previously known to be affected in reeler mutants that show a common migratory defect: the olivocochlear efferent neurons and the facial visceral motor nucleus. In control embryos, these cells migrate first toward a lateral position within the neural tube, and then parallel to the glial cell processes, to a ventral position where they settle close to the pial surface. In reeler mutants, the first migration is not affected, but the neurons are unable to reach the pial surface and remain in an ectopic position. Indeed, this is the first evidence that the migration of specific hindbrain nuclei can be divided into two parts: a reelin-independent and a reelin-dependent migration. We also show that reelin is expressed at high levels at the final destination of the migratory process, while the reelin intracellular effector Dab1 was expressed by cell groups that included the two populations affected. Mice mutant at the Dab1 locus, called scrambler, exhibit the same phenotype, a failure of final migration. However, examination of mice lacking both reelin receptors, ApoER2 and VLDLR, did not reveal the same phenotype, suggesting involvement of an additional reelin-binding receptor. In the hindbrain, reelin signaling might alter the adhesive properties of efferent neurons and their ability to respond to directional cues, as has been suggested for the migration of olfactory bulb precursors.
Key words: Reeler mutant, Dab1, Hindbrain, Neuronal migration
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