Axis Formation in Vertebrate Development

University Of California Berkeley, Berkeley CA

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Abstract

DESCRIPTION (provided by applicant): Our long term goal is to understand the signals that pattern the early vertebrate embryo, and particularly the role that BMP antagonists play in this process. We study this problem in both amphibians and mice, since each offers different experimental advantages. Xenopus laevis produces large numbers of eggs that are readily manipulated by injection and microsurgery. The combination of experimental embryology and molecular manipulation provide the tools to understand embryonic signaling at the molecular level. We also complement use of X. laevis with use of X. tropicalis, which offers the advantages of diploidy and a sequenced genome, both advantages for manipulating gene expression by Morpholino oligonucleotide-mediated knockdowns. Our work in the mouse has taken advantage of targeted mutations. The phenotypes of these mutations have suggested particular developmental contexts where BMP antagonists are crucial, and some of these contexts are particularly relevant to human developmental disorders. In the next grant period we will study how BMP antagonists implement important developmental decisions, either singly, or in overlapping combinations. These include the maintenance of neural stem cell populations and skeletal patterning in noggin mutants, and the induction and maintenance of somite differentiation in noggin/gremlin double mutants. Finally we will study the contribution of different BMP antagonists to formation of the dorsal ventral, and anterior posterior axes in the early embryo.