p66ShcA adaptor molecule accelerates ES cell neural induction

SHC genes codify for a family of adaptor molecules comprising four genes. Previous data have implicated the Shc(s) molecules in stem cell division and differentiation. Specifically, the p66ShcA isoform has been found to contribute to longevity and resistance from oxidative stress.Here we report that p66ShcA is up-regulated during in vitro neural induction in embryonic stem cells. p66ShcA over-expression in ES cells reduces GSK-3β kinase activation and increases β-catenin stabilization and its transcriptional activity. p66ShcA over-expression results in ES cells undergoing an anticipated neural induction and accelerated neuronal differentiation. Similar effects are obtained in human ES cells over-expressing p66ShcA.This study reveals a role for p66ShcA in the modulation of Wnt/β-catenin pathway and in ES cell neuralization which is consistent between mouse and human.