Early events in the development of the vertebrate myocardium and endoderm

In this dissertation, I describe some mechanisms by which pattern is translated into the formation of different tissues within the early vertebrate embryo. Using the molecular and genetic tools available in the study of zebrafish development, I have investigated the early development of the myocardium, the muscular layer of the heart, and the endoderm, the germ layer which gives rise to the gut. I have demonstrated that the faust locus encodes the zebrafish homolog of Gata5, an evolutionarily conserved zinc finger transcription factor. faust/gata5 mutants do not form functional hearts or guts. Further analysis of faust/ gata5 mutants revealed that Gata5 regulates the expression of several myocardial genes, including nkx2.5, a homolog of the Drosophila tinman gene. In the endoderm, Gata5 promotes endodermal differentiation and the formation of a normal complement of endodermal progenitors. When overexpressed gata5 can increase endodermal and myocardial gene expression and produce ectopic, rhythmically contracting myocardial tissue. These results indicate that Gata5 performs a unique and central role in the development of both myocardium and endoderm. Furthermore, through overexpression studies and mutant analysis, I have demonstrated that gata5 expression is induced by Nodal signaling, and that Gata5 acts in parallel with another transcription factor, Bon, to promote the differentiation of both the myocardium and endoderm. In addition to Nodal signals, Notch and Wnt signals are present in the germ ring during the formation of the endodermal progenitors. Overexpression experiments suggest that Wnt signaling promotes and Notch signaling antagonizes endoderm formation. Cumulatively, these results suggest that blastomeres form different tissues depending on the differential integration and interpretation of Nodal, Wnt and Notch signals.