Regulation of Sox9 function by SUMOylation in avian neural crest development

Abstract

Neural crest cells (NCCs) are one of the best-characterized and tractable experimental systems for studying cell fate specification, epithelial-mesenchymal transition (EMT), migration and differentiation. Moreover the similarity of EMT in NCCs and tumor metastasis suggests that understanding the molecular mechanisms of NCC EMT is likely to provide insight into how these programs are dysregulated during tumorigenesis. Our previous studies revealed that the transcription factor Sox9 is sufficient to promote several aspects of neural crest differentiation but Snail2 activity is also required for the disruption of neuroepithelial structure and acquisition of migratory behavior which characterizes NCC EMT. Here we report that Sox9 protein is SUMOylated in the developing chick neural tube and that abolishing this SUMOylation appears to inhibit its ability to initiate an EMT. We provide evidence that Snail2 contains a putative SUMO-interacting motif that may facilitate binding of Snail2 to SUMOylated Sox9 and explain why the two proteins are coordinately required for an EMT. In addition, we provide evidence that signals previously implicated in NCC delamination might regulate the SUMOylation status of Sox9. Together our studies suggest a molecular mechanism through which signaling pathways and post-translational modifications alter Sox9 activity to permit the elaboration of NCC development. Copyright © 2009 Published by Elsevier Ireland Ltd.