Mesoderm Formation in Vertebrate Embryos

Our research addresses the mechanisms by which the mesoderm of the vertebrate embryo is formed. Most of the work involves use of the amphibian species Xenopus laevis and Xenopus tropicalis, but we also make use of zebrafish embryos when appropriate. We are interested in studying mesoderm-inducing signals such as the nodal-related genes and derrière, in the signal transduction pathways used by these factors (especially the Smad proteins), and in the genes that are activated as immediate-early responses to induction. Transgenic Xenopus embryos are used to study how these immediate-early genes are regulated and to identify their targets. We are also making extensive use of morpholino anti-sense oligonucleotides to block gene function, both in Xenopus laevis and in the diploid species Xenopus tropicalis.

Much of our work concentrates on the Brachyury gene, which responds to mesoderm-inducing factors in a strict close-dependent fashion and which, when mis-expressed, can cause prospective ectodermal cells to form mesoderm. Brachyury is also required for the morphogenetic movements of gastrulation, and we have recently identified Wnt11 as a target of Brachyury which is required for gastrulation movements in both Xenopus and zebrafish. Future work will investigate the role of Wnt11 in gastrulation using cell biology and imaging techniques. We also plan to investigate the functions of other Brachyury targets such as members of the Bix family of homeodomain-containing proteins and genes that regulate the cell cycle.