Dr. BendeI-Stenzel is a pediatric nephrologist at the University of Minnesota. The candidate's long-term goal is an academic career devoted primarily to basic research in developmental nephrology and congenital kidney disease. Dr. Bendel-Stenzel has developed two lines of transgenic mice that utilize the Pax-2 promoter to drive the expression first of green fluorescent protein, and then Cre recombinase in the embryonic kidney. These mice will allow Dr. BendeI-Stenzel, under the direct mentorship of Dr. David Largaespada, to study the roles of catenins in kidney development. Alpha-and beta-catenin have both adhesion and signaling functions that have been shown to play important roles during embryogenesis. Their roles during the formation of the kidney, however, have not been established, as knockouts result in early embryonic lethality prior to the onset of kidney development. To overcome this obstacle, the candidate will utilize the Cre/Iox system. Dr. BendeI-Stenzel will first determine the function of alpha-catenin mediated adhesion and signaling during nephrogenesis by disrupting this molecule, first in the nephric duct, and then in the induced metanephric mesenchyme (Specific Aim 1). He will then determine the role of beta-catenin mediated signaling during early kidney development by employing a tissue specific knockout of this gene in the nephric duct (Specific Aim 2). The knowledge gained about the roles of catenin- mediated adhesion and signaling in early nephrogenesis may lead to new understandings about the molecular mechanisms of congenital renal disease.
