This application is being submitted in response to PAR-04-042 entitled """"""""Murine Atlas of Genitourinary Development."""""""" As stated, """"""""The genitourinary tract (GU) is the organ system most commonly affected by congenital birth defects, and many reports suggest that some of these birth defects (i.e. hypospadias and cryptorchidism) are increasing. Currently, GU developmental research is limited by a paucity of cell specific markers for key lineages within the developing GU tract, incomplete understanding of the normal three dimensional cellular structure of the major organs of the GU tract, incomplete understanding of the morphogenetic events that occur during organogenesis, and the lack of a detailed integrative database to assimilate complex temporal and spatial expression data."""""""" To address these deficiencies, we propose to first characterize the development of visceral smooth muscle associated with the murine GU tract using mice expressing fluorescent markers under the control of smooth muscle actin promoters. We will also generate an atlas of gene expression patterns that characterize distinct stages of differentiation in smooth muscle cells (SMCs) within GU tissues of the mouse. We will isolate highly enriched SMC populations from GU tissues using laser capture microdissection (LCM). It is expected that this approach will yield a high resolution analysis of gene expression in specimens of smooth muscle from a number of genitourinary tissues through developmental time. In combination with data generated by other projects within the consortium that will emerge from this funding initiative, this information is likely to provide clues regarding the molecular mechanisms involved in the development, maturation, and phenotypic modulation in GU SMCs as well as ultimately lead to the discovery of novel genes that are selectively expressed in GU SMCs and possibly in subsets of these cells. Insights regarding the cellular and molecular phenotype of GU smooth muscle will be invaluable for future research aimed at understanding the molecular basis of altered and diseased smooth muscle and to devise and evaluate strategies to repair or replace damaged organs.
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