Early requirement of the transcriptional activator Sox9 for neural crest specification in Xenopus

The neural crest is a multipotent population of cells that arises at the neural plate border in the vertebrate embryo. We have previously shown that a member of the Sox family of transcription factors, Sox9, is a regulator of neural crest formation in Xenopus, as Sox9-depleted embryos failed to form neural crest progenitors. Here, we describe experiments that further investigate Sox9 function during neural crest development. Induction of neural crest progenitors in Xenopus is regulated by Wnt signaling. We show that this process is largely dependent on Sox9 function as Wnt-mediated neural crest induction is inhibited in the context of Sox9-depleted embryos. Moreover, we demonstrate that Sox9 functions as a transcriptional activator during neural crest formation. Expression of a construct in which Sox9 DNA-binding domain (HMG box) is fused to the repressor domain of Drosophila engrailed blocked neural crest formation, thereby mimicking the phenotype of Sox9-depleted embryos. Finally, using a hormone-inducible inhibitory mutant of Sox9, lacking the transactivation domain, we show that Sox9 function is required for neural crest specification but not for its subsequent migration.