In the developing vertebrate brain, precerebellar neurons (PCNs) migrate from the dorsal hindbrain to the floor plate, stopping when they reach the ventral midline. This migration event is thought to be guided by Slit chemorepellants released from the floor plate and their Robo receptors expressed in the PCNs; however, previous studies relied on whole-organism knockouts of these broadly expressed genes. Now, Alain Chédotal and colleagues use conditional Slit and Robo knockouts, paired with tissue clearing and light sheet microscopy, to assay the effects of cell-specific gene inactivation on PCN migration (dev150375). Surprisingly, targeted loss of Robo receptors does not perturb migration: PCNs make it to and stop at the midline. Furthermore, targeted loss of Slit in the floor plate results in only a small subset of PCNs overshooting the midline, and loss of Slit from the facial nucleus has no effect. As targeted knockouts do not phenocopy whole-organism knockouts, the work demonstrates a non-cell-autonomous role for Slit and Robo molecules in PCN migration, and also raises the question of which chemorepellants other than Slit regulate the process.
