A role for the homeobox gene Xvex-1 as part of the BMP-4 ventral signalingpathway

BMP-4 is believed to play a central role in the patterning of the mesoderm by providing a strong ventral signal. As part of this ventral patterning si gnal, BMP-4 has to activate a number of transcription factors to fulfill th is role. Among the transcription factors regulated by BMP-4 are the Xvent a nd the GATA genes. A novel homeobox gene has been isolated termed Xvex-1 wh ich represents a new class of homeobox genes. Transcription of Xvex-1 initi ates soon after the midblastula transition. Xvex-1 transcripts undergo spat ial restriction from the onset of gastrulation to the ventral marginal zone , and the transcripts will remain in this localization including at the tai lbud stage in the proctodeum. Expression of Xvex-1 during gastrula stages r equires normal BMP-4 activity as evidenced from the injection of BMP-4, Sma d1, Smad5 and Smad6 mRNA and antisense BMP-4 RNA. Xvex-1 overexpression ven tralizes the Xenopus embryo in a dose dependent manner. Partial loss of Xve x-1 activity induced by antisense RNA injection results in the dorsalizatio n of embryos and the induction of secondary axis formation. Xvex-1 can resc ue the effects of overexpressing the dominant negative BMP receptor. These results place Xvex-1 downstream of BMP-4 during gastrulation and suggest th at it represents a novel homeobox family in Xenopus which is part of the ve ntral signaling pathway. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.