Sox9 and the Molecular Network Regulating Neural Crest Cell Motility

Abstract

The neural crest (NC) is one of the most characterized and accessible experimental systems to study the molecular regulation of cell migration. Our recent studies showed that phosphorylation of Sox9 is sufficient and required for NC delamination in the dorsal NC forming territory but how its transcriptional outcome leads to NC migratory behavior remains poorly understood. Here we found that Sox9 depends on Nedd9 function to mediate the transition of NC cells from delamination to migration via regulation of Rho family GTPase activities. Our data has revealed a novel molecular network for regulating NC motility. We have found that expression of Nedd9 (neural precursor cell expressed, developmentally downregulated), an intracellular scaffolding protein of the Cas family, can be induced by Sox9 regardless of its phosphorylation status, and In addition, Nedd9 function is mediated through recruiting a Rho GTPase activating protein, DLC1 (Deleted in liver cancer 1), which is induced by Sox9 but not Sox9S64A,S181A (non-phosphorylatable version of Sox9) and its close relative, Sox10. Altogether, our findings reveal mechanistic insights of a novel molecular network linking the transcriptional outcome of phosphorylated form of Sox9 and NC migratory behavior. Understanding the normal mechanisms of NC EMT will provide important clues on how such programs are dysregulated that lead to developmental defects.