Regulation of dorsal gene expression in Xenopus by the ventralizing homeodomain gene Vox.
Patterning in the vertebrate embryo is controlled by an interplay between signals from the dorsal organizer and the ventrally expressed BMPs. Here we examine the function of Vox, a homeodomain-containing gene that is activated by the ventralizing signal BMP-4. Inhibition of BMP signaling using a dominant negative BMP receptor (DeltaBMPR) leads to the ectopic activation of dorsal genes in the ventral marginal zone, and this activation is prevented by co-injection of Vox. chordin is the most strongly activated of those genes that are up-regulated by DeltaBMPR and is the gene most strongly inhibited by Vox expression. We demonstrate that Vox acts as a transcriptional repressor, showing that the activity of native Vox is mimicked by a Vox-repressor fusion (VoxEnR) and that a Vox-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 BMP-4 expression in whole embryos, we see no activation of BMP-4 by VoxG4A, demonstrating that this activation is indirect. Using a hormone-inducible version of VoxG4A, we find that a critical time window for Vox function is during the late blastula period. Using this construct, we demonstrate that only a subset of dorsal genes is directly repressed by Vox, revealing that there are different modes of regulation for organizer genes. Since the major direct target for Vox repression is chordin, we propose that Vox acts in establishing a BMP-4 morphogen gradient by restricting the expression domain of chordin.
Department of Biochemistry, University of Washington, Seattle, Washington, 98195-7350, USA.
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Melby
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Clements
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Kimelman
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D014981:Xenopus / Q000196:embryology* / Q000502:physiology*; D029867:Xenopus Proteins
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C099992:ventx2.1 protein, Xenopus