SARA regulates neuronal migration during neocortical development through L1 trafficking.

Emerging evidence suggests that endocytic trafficking of adhesion proteins plays a crucial role in neuronal migration during neocortical development. However, molecular insights into these processes remain elusive. Here, we study the early endosomal protein Smad anchor for receptor activation in the developing mouse brain. is enriched at the apical endfeet of radial glia of the neocortex. Although duanyu1800 knockdown did not lead to detectable neurogenic phenotypes, neurons exhibited impaired orientation and migration across the intermediate zone. Mechanistically, we show that duanyu1800 knockdown neurons exhibit increased surface expression of the L1 cell adhesion molecule. Neurons ectopically expressing L1 phenocopy the migration and orientation defects caused by duanyu1800 knockdown and display increased contact with neighboring neurites. L1 knockdown effectively rescues duanyu1800 suppression-induced phenotypes. duanyu1800 knockdown neurons eventually overcome their migration defect and enter later into the cortical plate. Nevertheless, these neurons localize at more superficial cortical layers than their control counterparts. These results suggest that duanyu1800 regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression.

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