Molecular regulation of neural crest development and melanoma metastasis

Abstract

Coordinated regulation of neural crest delamination is essential for its subsequent migration and differentiation into different derivatives. Our previous studies showed that Sox9, member of the SoxE family of transcription factors, is both sufficient and required for neural crest delamination in the dorsal neural crest forming territory but how its transcriptional outcome translates into neural crest migratory behavior remains poorly understood. We revealed that Sox9, but not its close relative, Sox10, is sufficient to induce ectopic expression of scaffolding protein, Nedd9. Epistasis analysis showed that Nedd9 functions downstream of Sox9 to mediate the transition of neural crest cells from delamination to migration. In addition, we also found a similar transcriptional regulation in melanoma metastasis consistent with its neural crest origin. Altogether, our findings reveal a novel and similar regulatory pathway in controlling both neural crest delamination and invasive behavior of melanoma. Our study also highlight the importance of understanding the molecular regulation of neural crest development that may provide insight into the underlying mechanisms of controlling neural crest-derived melanoma growth and metastasis for the future development of targeted drug therapies.