William J. McGinnis
Specification of Body Plan by Homeotic Proteins
Recent results from our lab and others on the functional specificity of homeotic proteins and homeotic target enhancers, strongly suggests that homeodomain/protein co-factor interactions underly and explain the ability of one homeotic protein to direct cells on a head developmental pathway, while another directs abdominal development. Based on our previous experiments on the function of mouse and human homeodomain proteins in Drosophila, we expect that some or many of the specific homeodomain/co-factor interactions will be conserved in mammals. So our goals are to identify these protein co-factors, characterize their interactions with homeotic proteins, and test for the evolutionary conservation of homologous factors in mammals.
Much of the current effort in the lab is directed at a large F2 enhancer/suppressor genetic screen to identify the genes encoding homeotic protein co-factors, specifically those factors involved in a posterior head-specific regulatory complex involving the Deformed homeotic protein. We believe that this screen is the surest method for the identification of these homeotic co-factors, but we are also attempting a variety of biochemical affinity approaches that may identify the factors more rapidly, but will not immediately address their biological relevance. The same screen also may identify biologically important downstream effector genes that mediate the morphogenetic functions of Deformed and other homeotic genes.