A novel function for the Xslug gene: control of dorsal mesendoderm development by repressing BMP-4

The Snail family of genes comprise a group of transcription factors with ch aracteristic zinc finger motifs. One of the members of this family is the S lug gene. Slug has been implicated in the development of neural crest in ch ick and Xenopus by antisense loss of function experiments. Here. we have ge nerated functional derivatives of Xslug by constructing cDNAs that encode t he Xslug protein fused with the transactivation domain of the virus-derived VP16 activator or with the repressor domain of the Drosophila Engrailed pr otein. Our results suggest that XSlug normally functions as a transcription al repressor and that Xslug-VP16 behaves as a dominant negative of Xslug. I n the present work, we confirm and extend previous results that suggest tha t Xslug has an important function in neural crest development, by controlli ng. its own transcription. In addition we have uncovered a new function for Xslug. We show that Xslug is expressed in the dorsal mesendoderm at the be ginning of gastrulation, where is it able to upregulate the expression of d orsal genes. On the other hand when Xslug is expressed outside of the organ izer it represses the expression of ventral genes. Our results indicate tha t this effect on mesodermal patterning depends on BMP activity, showing tha t Xslug can directly control the transcription of BMP-4. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.