The development of complex organs from pre-structural tissues is a mysterious process. Transdifferentiation and organ specialization depend on an interaction of biologic events which move rapidly in the assembly of structure-function relationships in the growing embryo. Cell differentiation is an active process and this suggests an on-line role for gene modulation. We believe that organ development depends on the participation and continuity of sequential sets of transcriptional proteins responding to morphogenic cues. Such developmental programs are restrictive, decisional, and usually tissue-specific. Very few pieces of this regulatory puzzle are known, and we believe a program project such as ours will cultivate new interdisciplinary research in this area. The projects in our program portfolio collectively bridge the disciplines of genetics and biochemistry with basic pathophysiology in support of six established research laboratories with common interest in the developmental biology of amniotes. Each of the project leaders come from diverse career pathways and bring special interactive strengths to the larger group. All of our projects are initially focused on rodents. Project 1 will identify new Kruppel-type zinc fingers expressed in the early stages of kidney development; Project 2 will focus on the comparison of genetic programs regulating hepatic development and regulation; Project 3 will investigate the effects of perturbations of Connexin 43 (Cx43) on the expression of gap junction proteins during the differentiation of nephrons; Project 4 will evaluate the role of forkhead domains in transcription factors that are active in early nephrogenesis; Project 5 will identify the genes important in the differentiation of adipose tissue using retinoic acid as a morphogen to probe the conversion of preadipocytes; and Project 6 will examine the molecular actions of caudal- related homeodomain proteins in the endoderm of developing intestine. Core units for project administration, molecular biology, and embryologic histochemistry will provide necessary and appropriate infrastructure. It is our hope and expectation that our work will successfully identify the positional coordinates for some important regulatory events by beginning an intensive study of significant genes in early organ development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK049210-05
Application #
2905705
Study Section
Special Emphasis Panel (SRC (04))
Program Officer
Sato, Sheryl M
Project Start
1995-09-01
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2001-08-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Juliana, Christine A; Yang, Juxiang; Cannon, Corey E et al. (2018) A PDX1-ATF transcriptional complex governs ? cell survival during stress. Mol Metab 17:39-48
Barnoud, Thibaut; Budina-Kolomets, Anna; Basu, Subhasree et al. (2018) Tailoring Chemotherapy for the African-Centric S47 Variant of TP53. Cancer Res 78:5694-5705
Kim, Yong Hoon; Marhon, Sajid A; Zhang, Yuxiang et al. (2018) Rev-erb? dynamically modulates chromatin looping to control circadian gene transcription. Science 359:1274-1277
Plikus, Maksim V; Guerrero-Juarez, Christian F; Ito, Mayumi et al. (2017) Regeneration of fat cells from myofibroblasts during wound healing. Science 355:748-752
Juliana, Christine A; Yang, Juxiang; Rozo, Andrea V et al. (2017) ATF5 regulates ?-cell survival during stress. Proc Natl Acad Sci U S A 114:1341-1346
Ediger, Benjamin N; Lim, Hee-Woong; Juliana, Christine et al. (2017) LIM domain-binding 1 maintains the terminally differentiated state of pancreatic ? cells. J Clin Invest 127:215-229
Jang, Jessica C; Li, Jiang; Gambini, Luca et al. (2017) Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction. Proc Natl Acad Sci U S A 114:E10399-E10408
Carr, Rotonya M; Dhir, Ravindra; Mahadev, Kalyankar et al. (2017) Perilipin Staining Distinguishes Between Steatosis and Nonalcoholic Steatohepatitis in Adults and Children. Clin Gastroenterol Hepatol 15:145-147
Park, Hyeong Kyu; Kwak, Mi Kyung; Kim, Hye Jeong et al. (2017) Linking resistin, inflammation, and cardiometabolic diseases. Korean J Intern Med 32:239-247
Ackermann, Amanda M; Zhang, Jia; Heller, Aryel et al. (2017) High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting. Mol Metab 6:236-244

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