Non-cell autonomous control of precerebellar neuron migration by Slits and Robos

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 was previously 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 Robo1/2 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 Slits 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 Slits in the facial nucleus is dispensable for pontine neuron migration. Together, these results show that Robo1/2 receptors act non-cell autonomously in migrating precerebellar neurons, and that floor plate signals, other than Slits, should exist to prevent midline crossing.