It is proposed to construct a computational model which precisely describes the genomic regulatory apparatus required for endomesoderm specification in sea urchin embryos. The model is to be couched in terms of specific, experimentally verifiable or falsifiable predictions that define necessary inputs and outputs of key cis regulatory elements. These are elements which control expression in time and space of genes encoding transcription factors and certain signaling components, which other evidence has identified as relevant genes required in the process of endomesoderm specification. A first stage model of this kind has been built. The investigators will carry out kinetic measurements required to ascertain logical interrelations within the relevant cis regulatory systems and other experiments designed to test architectural features of the computational model. These studies will examine the predicted effects of target site mutations on spatial expression of genes involved in endomesoderm specification, under specific conditions of perturbation. They will also generate a 3D digital construction of the embryo through time, using confocal imaging data, and impose on it the gene expression profiles predicted by the computational regulatory model. The model will ultimately constitute a quantitative computational analysis of a genomic regulatory network, defined at the DNA sequence level, the function of which is to organize a complex, major process in animal development.
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