Perception of our environment entirely depends on the close interaction between the central and peripheral nervous system. In order to communicate each other, both systems must develop in parallel and in coordination. During development, axonal projections from the CNS as well as the PNS must extend over large distances to reach their appropriate target cells. To do so, they read and follow a series of axon guidance molecules. Interestingly, while these molecules play critical roles in guiding developing axons, they have also been shown to be critical in other major neurodevelopmental processes, such as the migration of cortical progenitors. Currently, a major hurdle for brain repair after injury or neurodegeneration is the absence of axonal regeneration in the mammalian CNS. By contrasts, PNS axons can regenerate. Many hypotheses have been put forward to explain this paradox but recent studies suggest that hacking neurodevelopmental mechanisms may be the key to promote CNS regeneration. Here we provide a seminar report written by trainees attending the second Flagship school held in Alpbach, Austria in September 2018 organized by the International Society for Neurochemistry (ISN) together with the Journal of Neurochemistry (JCN). This advanced school has brought together leaders in the fields of neurodevelopment and regeneration in order to discuss major keystones and future challenges in these respective fields.

Inferior olivary (IO) neurons are born in the dorsal hindbrain and migrate tangentially toward the ventral midline. During their dorsoventral migration, IO neurons extend long leading processes that cross the midline, transform into axons, and project into the contralateral cerebellum. In absence of the axon guidance receptor Robo3, IO axons fail to cross the midline and project to the ipsilateral cerebellum. Remarkably, the IO cell bodies still reach the midline where they form a nucleus of abnormal cytoarchitecture. The mechanisms underlying the migration of Robo3-deficient IO neurons are unknown. Here, we used three-dimensional imaging and transgenic mice to label subsets of IO neurons and study their migratory behavior in Robo3 knockout. We show that IO migration is delayed in absence of Robo3. Strikingly, Robo3-deficient IO neurons progress toward the midline in a direction opposite to their axons. This occurs through a change of polarity and the generation of a second leading process at the rear of the cell. These results suggest that Robo3 receptor controls the establishment of neuronal polarity and the coupling of axonogenesis and cell body migration in IO neurons.