Nyap1 Regulates Multipolar-Bipolar Transition and Morphology of Migrating Neurons by Fyn Phosphorylation during...

The coordination of cytoskeletal regulation is a prerequisite for proper neuronal migration during mammalian corticogenesis. Neuronal tyrosine-phosphorylated adaptor for the phosphoinositide 3-kinase 1 (Nyap1) is a member of the Nyap family of phosphoproteins, which has been studied in neuronal morphogenesis and is involved in remodeling of the actin cytoskeleton. However, the precise role of Nyap1 in neuronal migration remains unknown. Here, overexpression and knockdown of Nyap1 in the embryonic neocortex of mouse by in utero electroporation-induced abnormal morphologies and multipolar-bipolar transitions of migrating neurons. The level of phosphorylated Nyap1 was crucial for neuronal migration and morphogenesis in neurons. Furthermore, Nyap1 regulated neuronal migration as a downstream target of Fyn, a nonreceptor protein-tyrosine kinase that is a member of the Src family of kinases. Importantly, Nyap1 mediated the role of Fyn in the multipolar-bipolar transition of migrating neurons. Taken together, these results suggest that cortical radial migration is regulated by a molecular hierarchy of Fyn via Nyap1.