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 BAC-mediated transgenics to express fluorescent reporter proteins and Cre recombinase in specific cell populations for cell marking, cell fate and genetic manipulation studies.
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