This proposal outlines the use of the chick gastrointestinal tract (gut) as a model system to study the molecular controls of visceral development. The gut is formed by invaginations at both anterior and posterior embryonic poles. Subsequent elongation, folding and cellular differentiation result in a closed tube with gross morphological and functional distinctions along the anterior/posterior (AP) axis. This AP axis is regionalized to form the adult gut morphology of a fore-, and mid- and hind-gut Endoderm/mesoderm (EM) signals are essential in both the initiation and morphogenesis of gut tube development and in forming gut derivatives (e.g. pancreas and lung). This proposal addresses the molecular controls of the AP gut pattern. Several homologs of regulatory genes in Drosophila gut development are expressed in the vertebrate gut in patterns indicative of potential functional conservation, including the Hox genes.
Specific Aims are designed to study this hypothesis: Hox genes play a key regulatory role in setting up the gross, microscopic, and molecular pattern of the vertebrate gut. Exploiting the facility of the chick system, virally mediated mis- expression studies in ovo and in organ expands will experimentally address the above hypothesis. The studies will focus on the importance of the Abd- B class of Hox genes in their role in patterning the distal mid-gut and hind-gut. Comparison will be made of the mesodermal versus endodermal roles of specific Hox genes (the 13th paralog) in patterning the gross and microscopic morphology and cellular differentiation of the posterior region of the gut. Studies are designed to elucidate potential interactions of these Hox genes and candidate factors (e.g. Wnt5a CdxA) and are specifically focused on understanding their role in EM signaling in gut development. Included are studies designed to determine the regional splanchnic mesenchymal specificity of Hox gene function in gut development.
