? 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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK070219-04
Application #
7435371
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (O2))
Program Officer
Hoshizaki, Deborah K
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$976,374
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Georgas, Kylie M; Armstrong, Jane; Keast, Janet R et al. (2015) An illustrated anatomical ontology of the developing mouse lower urogenital tract. Development 142:1893-908
Keil, Kimberly P; Abler, Lisa L; Laporta, Jimena et al. (2014) Androgen receptor DNA methylation regulates the timing and androgen sensitivity of mouse prostate ductal development. Dev Biol 396:237-45
Wiese, Carrie B; Fleming, Nicole; Buehler, Dennis P et al. (2013) A Uchl1-Histone2BmCherry:GFP-gpi BAC transgene for imaging neuronal progenitors. Genesis 51:852-61
Keil, Kimberly P; Altmann, Helene M; Mehta, Vatsal et al. (2013) Catalog of mRNA expression patterns for DNA methylating and demethylating genes in developing mouse lower urinary tract. Gene Expr Patterns 13:413-24
Keil, Kimberly P; Mehta, Vatsal; Abler, Lisa L et al. (2012) Visualization and quantification of mouse prostate development by in situ hybridization. Differentiation 84:232-9
Buehler, Dennis P; Buehler, Dennis; Wiese, Carrie B et al. (2012) An optimized procedure for fluorescence-activated cell sorting (FACS) isolation of autonomic neural progenitors from visceral organs of fetal mice. J Vis Exp :e4188
Keil, Kimberly P; Mehta, Vatsal; Branam, Amanda M et al. (2012) Wnt inhibitory factor 1 (Wif1) is regulated by androgens and enhances androgen-dependent prostate development. Endocrinology 153:6091-103
Jameson, Samantha A; Natarajan, Anirudh; Cool, Jonah et al. (2012) Temporal transcriptional profiling of somatic and germ cells reveals biased lineage priming of sexual fate in the fetal mouse gonad. PLoS Genet 8:e1002575
Abler, Lisa L; Mehta, Vatsal; Keil, Kimberly P et al. (2011) A high throughput in situ hybridization method to characterize mRNA expression patterns in the fetal mouse lower urogenital tract. J Vis Exp :
Mehta, Vatsal; Abler, Lisa L; Keil, Kimberly P et al. (2011) Atlas of Wnt and R-spondin gene expression in the developing male mouse lower urogenital tract. Dev Dyn 240:2548-60

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