COUP-TFs (Chicken Ovalbumin Upstream Promoter-Transcription Factors) are members of the Steroid/Thyroid Hormone Receptor superfamily. Since their ligand is not known, they are classified as orphan receptors. Molecular biology studies indicate that they are negative regulators which can inhibit the basal promoter activity of many genes as well as interfere with many transcription activators such as thyroid hormone, retinoic acid, vitamin D. estrogen. retinoid X, and peroxisome proliferator activated receptors. To dissect the physiological roles of the COUP-TFs, we have carried out expression studies of the COUP-TFs during mouse embryonic development. These studies support the hypothesis that COUP-Tfs are important for the cell type specific differentiation in central nervous system and they also play a primordial role in epithelial-mesenchymal interactions during organogenesis of lung, kidney, prostate, skin, salivary gland, pancreases and gastrointestinal organs. In this application, we propose experiments to verity these hypotheses. Specifically, we will use homologous recombination to knock-out the COUP- TFI and II genes either in the whole animal or in a few specific tissues to study their role(s) during development and differentiation of the central nervous system as well as various organs. In addition, we will use an in vitro reconstitution system between mesenchymal and epithelial cells to confirm that COUP-TFs indeed are involved in regulating the paracrine signals necessary for the mesenchymal epithelial interactions. Finally, we will also determine the signals regulating the COUP-TF expression during embryonic development. These studies should help us to realize our long-term goals in understanding the signaling pathways which require the involvement of the COUP-TF gene activities eventually resulting in the final cellular differentiation of various tissues. It is expected that the understanding derived from this project will be relevant to the biology of development and differentiation. The proposed studies should also be pertinent to development of more precise theories for the biochemical mechanism of action of hormones in general and more specifically thyroid, retinoic acid and vitamin D.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK045641-06
Application #
2545702
Study Section
Endocrinology Study Section (END)
Program Officer
Margolis, Ronald N
Project Start
1992-09-30
Project End
1999-09-29
Budget Start
1997-09-30
Budget End
1998-09-29
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Wetendorf, Margeaux; Wu, San-Pin; Wang, Xiaoqiu et al. (2017) Decreased epithelial progesterone receptor A at the window of receptivity is required for preparation of the endometrium for embryo attachment. Biol Reprod 96:313-326
Zhao, Fei; Franco, Heather L; Rodriguez, Karina F et al. (2017) Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice. Science 357:717-720
Xie, Xin; Wu, San-Pin; Tsai, Ming-Jer et al. (2017) The Role of COUP-TFII in Striated Muscle Development and Disease. Curr Top Dev Biol 125:375-403
Lee, Hui-Ju; Kao, Chung-Yang; Lin, Shih-Chieh et al. (2017) Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development. Sci Rep 7:3136
Wang, Leiming; Xu, Mafei; Qin, Jun et al. (2016) MPC1, a key gene in cancer metabolism, is regulated by COUPTFII in human prostate cancer. Oncotarget 7:14673-83
Xie, Xin; Tsai, Sophia Y; Tsai, Ming-Jer (2016) COUP-TFII regulates satellite cell function and muscular dystrophy. J Clin Invest 126:3929-3941
Wu, San-Pin; Yu, Cheng-Tai; Tsai, Sophia Y et al. (2016) Choose your destiny: Make a cell fate decision with COUP-TFII. J Steroid Biochem Mol Biol 157:7-12
Lin, Shih-Chieh; Kao, Chung-Yang; Lee, Hui-Ju et al. (2016) Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer. Nat Commun 7:11418
Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming et al. (2015) Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure. Nat Commun 6:8245
Tang, Ke; Tsai, Sophia Y; Tsai, Ming-Jer (2015) COUP-TFs and eye development. Biochim Biophys Acta 1849:201-9

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