Snail-related transcriptional repressors are required in Xenopus for both the induction of the neural crest and its subsequent migration

The neural crest is a transient population of precursor cells that arises a t the border between the neural plate and prospective epidermis in vertebra te embryos. The earliest known response to neural-crest-inducing signals is the expression of the zinc-finger transcription factors slug and snail. Al though it is widely believed that these transcription factors play an essen tial role in neural crest development, relatively little is understood abou t their mechanism of action during this process. We have previously shown t hat overexpression of XSlug leads to expanded expression of neural crest ma rkers and an excess of at least one neural crest derivative, melanocytes. I n order to further investigate XSlug function, we overexpressed mutant cons tructs in which the DNA-binding domain was fused to either the activation d omain from Gal4 or the repressor domain from Drosophila Engrailed. The Engr ailed repressor fusion was found to mimic the effects of wild-type XSlug, i ndicating that XSlug functions as a transcriptional repressor during neural crest formation. In contrast, overexpression of either the activation doma in fusion or the DNA-binding domain alone was found to inhibit XSlug functi on. Using a hormone-inducible inhibitory mutant, we show that inhibition of XSlug function at early stages prevents the formation of neural crest prec ursors, while inhibition at later stages interferes with neural crest migra tion, demonstrating for the first time that this transcriptional repressor is required during multiple stages of neural crest development. (C) 2000 Ac ademic Press.