The vertebrate embryo is patterned by opposing signals that originate both dorsally and ventrally in the gastrula. This proposal examines the role of Vox, a Xenopus homeobox gene that is positively regulated by the ventral signaling molecule BMP-4. Overexpression of Vox causes embryos to become ventralized, and suppresses dorsal gene expression. Vox is expressed in a similar pattern to BMP-4, and therefore it might be a downstream mediator of BMP-4. However, Vox overexpression causes increased BMP-4 levels. Thus, Vox might act to stabilize BMP-4 expression via an autoregulatory loop, without activating genes that are targets of BMP-4.
My first aim i s to understand how Vox fits in the regulatory hierarchy of ventral specification. To determine whether Vox acts downstream of BMP-4, I will see if injected Vox RNA can activate targets of BMP-4 in embryos where BMP-4 signaling is blocked by overexpression of a dominant-negative BMP receptor.
My second aim i s to determine the requirements for Vox during development. I will examine how development and gene expression patterns are affected in embryos injected with a dominant negative Vox mutant.
| Melby, A E; Clements, W K; Kimelman, D (1999) Regulation of dorsal gene expression in Xenopus by the ventralizing homeodomain gene Vox. Dev Biol 211:293-305 |
