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Publication : Uncoupling axon guidance and neuronal migration in Robo3-deficient inferior olivary neurons.

First Author  Moreno-Bravo JA Year  2022
Journal  J Comp Neurol Volume  530
Issue  16 Pages  2868-2880
PubMed ID  35811330 Mgi Jnum  J:331583
Mgi Id  MGI:7388683 Doi  10.1002/cne.25381
Citation  Moreno-Bravo JA, et al. (2022) Uncoupling axon guidance and neuronal migration in Robo3-deficient inferior olivary neurons. J Comp Neurol 530(16):2868-2880
abstractText  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.
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