The control of precerebellar neuron migration by RNA-binding protein Csde1

Abstract

Neuronal migration during brain development sets the position of neurons for the subsequent wiring of neural circuits. To understand the molecular mechanism regulating the migrating process, we considered the migration of mouse precerebellar neurons. Precerebellar neurons originate in the rhombic lip of the hindbrain and show stereotypic, long-distance tangential migration along the circumference of the hindbrain to form precerebellar nuclei at discrete locations. To identify the molecular components underlying this navigation, we screened for genes expressed in the migrating precerebellar neurons. As a result, we identified the following three genes through the screening; Calm1, Septin 11, and Csde1. We report here functional analysis of one of these genes, Csde1, an RNA-binding protein implicated in the post-transcriptional regulation of a subset of cellular mRNA, by examining its participation in precerebellar neuronal migration. We found that shRNA-mediated inhibition of Csde1 expression resulted in a failure of precerebellar neurons to complete their migration into their prospective target regions, with many neurons remaining in migratory paths. Furthermore, those that did reach their destination failed to invade the depth of the hindbrain via radial migration. These results have uncovered a crucial role of Csde1 in the proper control of both radial and tangential migration of precerebellar neurons.