Regulation of dorsal gene expression in Xenopus by the ventralizing homeodomain gene Vox

Patterning in the vertebrate embryo is controlled by an interplay between s ignals from the dorsal organizer and the ventrally expressed BMPs. Here we examine the function of Vex, a homeodomain-containing gene that is activate d by the ventralizing signal BMP-4. Inhibition of BMP signaling using a dom inant negative BMP receptor (Delta BMPR) leads to the ectopic activation of dorsal genes in the ventral marginal zone, and this activation is prevente d by co-injection of Vex. chordin is the most strongly activated of those g enes that are up-regulated by Delta BMPR and is the gene most strongly inhi bited by Vox expression. We demonstrate that Vox acts as a transcriptional repressor, showing that the activity of native Vox is mimicked by a Vex-rep ressor fusion (VoxEnR) and that a Vex-activator fusion (VoxG4A) acts as an antimorph, causing the formation of a partial secondary axis when expressed on the ventral side of the embryo. Although Vox can ectopically activate B MP-4 expression in whole embryos, we see no activation of BMP-4 by VoxG4A, demonstrating that this activation is indirect. Using a hormone-inducible v ersion of VoxG4A, we find that a critical time window for Vox function is d uring the late blastula period. Using this construct, we demonstrate that o nly a subset of dorsal genes is directly repressed by Vex, revealing that t here are different modes of regulation for organizer genes. Since the major direct target for Vox repression is chordin, we propose that Vox acts in e stablishing a BMP-4 morphogen gradient by restricting the expression domain of chordin. (C) 1999 Academic Press.