The morphogenetic movements of vertebrate gastrulation and concomitant induction of mesoderm are well characterized in organisms such as Xenopus, chick and mouse. Due to the accessibility and ease of in vitro and in vivo manipulation of the Xenopus embryo, a number of molecules with potential roles in mesoderm induction and organization have been identified. However, one limitation facing experiments with amphibian or chick is the absence of mutations; and in many cases, it is unknown whether these identified molecules are part of an endogenous mesoderm production pathway or if they simply simulate the normal embryonic mesoderm induction mechanism. The ability to induce mutations in the mouse provides an advantage for studying the complex interactions during gastrulation on a defined genetic background. The fate map of the early mouse gastrula is similar to that of Xenopus and chick, and homologues of molecules implicated in Xenopus mesoderm induction are also temporally and spatially expressed during mouse gastrulation. Thus, the underlying control of this process is likely to be conserved amongst vertebrates. The experiments outlined in this proposal focus on a series of radiation- induced deletions which identify through complementation and embryological studies regions of mouse chromosome 7 containing genes needed for gastrulation and mesoderm organization.
The specific aims concentrate on molecular approaches for identifying and evaluating the functional significance of candidate genes as well as a continued analysis of the biology of the mutations.
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