HOMEOBOX GENES AND THEIR TARGETS IN XENOPUS DEVELOPMENT

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Homeobox genes encode DNA-binding proteins that control key steps in animal development. Spemann and Mangold (1924) identified the dorsal lip of the blastopore, the organizer, as a region of the embryo able to induce twinning, or a secondary body axis, when transplanted to a host embryo. Recent experiments indicate that homeobox genes, such as goosecoid and Xnot-2, play an important role in the organizer phenomenon. Microinjection of goosecoid mRNA can mimic Spemann's experiment, recruiting neighboring cells into twinned axes in Xenopus. Because homeobox genes encode nuclear proteins, their effects on neighboring cells must be mediated by secreted molecules. We have recently identified the two major downstream targets activated by organizer homeobox genes: chordin and cerberus. Both are novel secreted proteins. In addition, goosecoid represses the expression of BMP-4, a ventralizing signal that is antagonized by the chordin protein. By studying organizer-specific homeobox genes and their secreted targets chordin, cerberus and BMP-4 we hope to better understand the molecular mechanisms that pattern vertebrate development. In particular, we will ask how these genes pattern the three germ layers, the mesoderm, the ectoderm and the endoderm, and how they control the sequential deployment of Hox genes in the antero-posterior body axis. Because the molecular mechanisms of development are very conserved, these studies in Xenopus should provide insights into the molecules that control development in all vertebrates, including humans.