FMRP regulates neuronal migration via MAP1B

Abstract

The Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability, and the first monogenic cause of Autism Spectrum Disorder. FXS is caused by the absence of the RNA-binding protein FMRP (Fragile X Messenger Ribonucleoprotein). Neuronal migration is an essential step of brain development allowing displacement of neurons from their germinal niches to their final integration site. The precise role of FMRP in neuronal migration remains mostly unexplored. We studied the consequences of FMRP absence on migration, by live-imaging neurons of the postnatal Rostral Migratory Stream (RMS). In Fmr1-null RMS, neurons exhibit a slowed-down migration and an impaired trajectory, associated with defects of their centrosomal movement. RNA-interference-induced knockdown of Fmr1 shows that these migratory defects are cell-autonomous. Finally, the FMRP mRNA target involved in these defects is MAP1B (Microtubule-Associated Protein 1B), since its knockdown rescues most migratory defects. Our results thus unveil a new neurodevelopmental role of FMRP, as a crucial actor of neuronal migration linked to MAP1B, potentially important for the understanding of FXS pathophysiology.