Cloning/characterization of novel downstream targets & expression/functional analysis of Hoxa2

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Homeobox proteins are powerful regulators of morphogenetic processes and important determinants of the anterior-posterior axis during development.  Members of the homeobox gene family are primarily recognized by the presence of a 60 amino acid DNA binding region, the homeodomain. The homeodomain has a helix-turn-helix motif that binds to specific nucleotide sequences in DNA thereby enhancing or suppressing the expression of the corresponding target genes. The long-term goal of my research program is to characterize the function of new Hoxa2 downstream target genes (Tasp and Dyrk4) isolated in my lab by chromatin immunoprecipitation (ChIP). In particular, our focus is to identify what functional role they play in concert with Hoxa2 in the visual system and in palatogenesis. The specific aims of the present proposed research are: 1. Characterize in vivo and in vitro binding specificity of Hoxa2 downstream targets; 2. Functional analysis of Hoxa2 and its downstream targets in the neural retina; and 3. Identify mechanism(s) involved in cleft palate development in Hoxa2-/-mice. Characterizing the functional role of Hoxa2 and its the downstream targets will decipher the mechanism(s) that allow Hoxa2 to act in multiple germ layers to mediate neural retina differentiation and palatogenesis. This research will advance our understanding of the role of Hoxa2 in normal vision and in cleft palate formation (a common human birth defect).