info:eu-repo/semantics/article
Sara regulates neuronal migration during neocortical development through L1 trafficking
Fecha
2016-09Registro en:
Mestres Lascano, Ivan; Chuang, Jen-Zen; Calegari, Federico; Conde, Cecilia Beatriz; Sung, Ching-Hwa; Sara regulates neuronal migration during neocortical development through L1 trafficking; Company of Biologists; Development; 143; 17; 9-2016; 3143-3153
0950-1991
1477-9129
CONICET Digital
CONICET
Autor
Mestres Lascano, Ivan
Chuang, Jen-Zen
Calegari, Federico
Conde, Cecilia Beatriz
Sung, Ching-Hwa
Resumen
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 (SARA) in the developing mouse brain. SARA is enriched at the apical endfeet of radial glia of the neocortex. Although SARA knockdown did not lead to detectable neurogenic phenotypes, SARA-suppressed neurons exhibited impaired orientation and migration across the intermediate zone. Mechanistically, we show that SARA knockdown neurons exhibit increased surface expression of the L1 cell adhesion molecule. Neurons ectopically expressing L1 phenocopy the migration and orientation defects caused by SARA knockdown and display increased contact with neighboring neurites. L1 knockdown effectively rescues SARA suppressioninduced phenotypes. SARA 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 SARA regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression.