The Xvex-1 antimorph reveals the temporal competence for organizer formation and an early role for ventral homeobox genes

The organizer in vertebrate embryos has been shown to play a central role in their development by antagonizing ventralizing signals and promoting dorsal development. The ventral homeobox gene, Xvex-1, is capable of fulfilling some of the functions of BMP-4. By fusion to activation and repression domains, Xvex-1 was shown to function as a repressor of transcription. The activator version of Xvex-1, the antimorph, was made inducible by fusion to the ligand binding domain of the glucocorticoid receptor. The organizer genes, gsc and Otx-2, were identified as direct targets of Xvex-1. The XVEX-1 antimorph can induce the formation of secondary axes. Temporal analysis of secondary axis induction revealed that the competence to induce a secondary organizer ends with the onset of gastrulation. The same temporal competence window was exhibited by an inducible gsc construct. Partial loss of Xvex-1 activity was able to improve the efficiency of secondary axis induction by the dominant negative BMP receptor or Smad6. These observations together with the early widespread expression of Xvex-1 throughout the embryo prior to gastrulation encoding a homeodomain repressor protein, suggest that elements of the ventral signaling pathway play an important role during late blastula in restricting the formation of Spemann's organizer. Copyright (C) 2000 Elsevier Science Ireland Ltd.