HARVARD COLLEGE, PRESIDENT & FELLOWS OF
Kidney disease is one of the leading health-care costs. Despite the vital importance of the kidney to maintaining the normal physiological equilibrium of an individual, there is a relatively poor understanding of the developmental program that creates the functional organ. Our goal is to generate a detailed spatial map of the cellular expression of selected regulatory genes during mammalian (mouse) kidney development to generate a "molecular anatomy" of the developing kidney. We will also create a series of transgenic mouse strains that will allow the ready identification and genetic manipulation of key cell types. Aim 1: We will perform a genome-wide analysis of the expression of all genes encoding mouse transcriptional regulators, ligands and cognate surface receptors in the embryonic urogenital system. Aim 2: We will generate a high resolution section in situ hybridization (SISH) map of the expression of all genes in Aim 1 in the fetal and neonatal kidney. Aim 3: We will perform transcriptional array analysis of renal tubule deficient mouse kidneys and micro-dissected kidney tubules to identify, and subsequently map the expression of tubule specific genes. Aim 4: We will use bacterial artificial chromosome (BAC)-mediated transgenics to express fluorescent reporter proteins and Cre recombinase in specific cell populations for cell marking, cell fate and genetic manipulation studies.