REGULATION OF HOX GENE-EXPRESSION AND POSTERIOR DEVELOPMENT BY THE XENOPUS CAUDAL HOMOLOG XCAD3

The caudal gene codes for a homeodomain transcription factor that is r equired for normal posterior development in Drosophila, In this study the biological activities of the Xenopus caudal (Cdx) family member Xc ad3 are examined. A series of domain-swapping experiments demonstrate that the N-terminus of Xcad3 is necessary for it to activate Hox gene expression and that this function can be replaced by the activation do main from the viral protein VP16. In addition, experiments using an Xc ad3 repressor mutant (XcadEn-R), which potently blocks the activity of wild-type Xcad3, are reported. Overexpression of XcadEn-R in embryos inhibits the activation of the same subset of Hox genes that are activ ated by wildtype Xcad3 and leads to a dramatic disruption of posterior development. We show that Xcad3 is an immediate early target of the F GF signalling pathway and that Xcad3 posteriorizes anterior neural tis sue in a similar way to FGF. Furthermore, Xcad3 is required for the ac tivation of Hox genes by FGFs. These data provide strong evidence that Xcad3 is required for normal posterior development and that it regula tes the expression of the Hox genes downstream of FGF signalling.