Nedd9 makes multipotent neural crest cells motile

AQUINO JB

Chiclayo

Jornada; VI Jornada Internacional de Genética ?66 years of 46 Human Chromosomes? Últimos Avances en Genética y Biología Molecular; 2022

The International Circle of Genetic Studies

Cell migration is essential for the development of numerous structures derived from embryonic neural crest cells (NCCs); however, the underlying molecular mechanisms are not fully understood. NCCs are highly migratory multipotent cells and contribute to many different cell types, including peripheral neurons, glia and pigment cells. In the present work we report expression of Nedd9, a scaffolding protein within the integrin signaling pathway, in progenitor cells of different tissues including NCCs. In particular, Nedd9 was found to be expressed in the dorsal neural tube at the time of neural crest delamination and in early migrating NCCs. To analyze the role of Nedd9 in neural crest development we performed loss- and gain-of-function experiments and examined the subsequent effects on delamination and migration in vitro and in vivo. Our results demonstrate that loss of Nedd9 activity in chick NCCs perturbs cell spreading and the density of focal complexes and actin filaments, properties known to depend on integrins. Moreover, a siRNA dose-dependent decrease in Nedd9 activity results in a graded reduction of NCC's migratory distance while forced overexpression increases it. Retinoic acid (RA) was found to regulate Nedd9 expression in NCCs. Our results demonstrate in vivo that Nedd9 promotes the migration of NCCs in a graded manner and suggest a role for RA in the control of Nedd9 expression levels.