ABSTRACT
During development, precerebellar neurons migrate tangentially from the dorsal hindbrain to the floor plate. Their axons cross it but their cell bodies stop their ventral migration upon reaching the midline. It has previously been shown that Slit chemorepellents and their receptors, Robo1 and Robo2, might control the migration of precerebellar neurons in a repulsive manner. Here, we have used a conditional knockout strategy in mice to test this hypothesis. We show that the targeted inactivation of the expression of Robo1 and Robo2 receptors in precerebellar neurons does not perturb their migration and that they still stop at the midline. The selective ablation of the expression of all three Slit proteins in floor-plate cells has no effect on pontine neurons and only induces the migration of a small subset of inferior olivary neurons across the floor plate. Likewise, we show that the expression of Slit proteins in the facial nucleus is dispensable for pontine neuron migration. Together, these results show that Robo1 and Robo2 receptors act non-cell autonomously in migrating precerebellar neurons and that floor-plate signals, other than Slit proteins, must exist to prevent midline crossing.
Footnotes
Author contributions
Conceptualization: A.C.; Methodology: C.D., Q.R., P.Z., S.F., A.C.; Validation: S.F., A.C.; Formal analysis: C.D., Q.R., P.Z., A.C.; Investigation: C.D., Q.R., P.Z., S.F., A.C.; Resources: A.C.; Data curation: C.D., Q.R., P.Z., S.F., A.C.; Writing - original draft: A.C.; Writing - review & editing: C.D., P.Z., A.C.; Visualization: A.C.; Supervision: A.C.; Project administration: A.C.; Funding acquisition: A.C.
Funding
C.D. was a recipient of a fellowship from the Fondation pour la Recherche Médicale (FRM). This work was supported by grants from the Fondation pour la Recherche Médicale (DEQ20120323700), the Agence Nationale de la Recherche (ANR-14-CE13-0004-01). It was performed in the frame of the Labex Lifesenses (ANR-10-LABX-65) supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir programme (ANR-11-IDEX-0004-02).