Kidney development is largely the result of a unique cellular transdifferentiation event wherein metanephric mesenchymal cells become epithelial cells which form the glomerulus and tubules of mature nephrons. These events are initiated by a poorly understood reciprocal inductive interaction between epithelial cells of the ureteric bud and the proliferating mesenchyme. These dramatic cellular differentiation events during nephrogenesis must require a considerable reprogramming of gene expression in the nucleus and therefore must be mediated in part by a set of kidney-specific transcription factors. However, little is currently known about transcription factors in the kidney which function specifically to mediate the mesenchymal-epithelial transition and/or maintain the differentiated phenotype. The forkhead domain family of transcription factors share a highly conserved approximately 110 amino acid motif which mediates sequence- specific DNA binding. Almost all known forkhead -domain containing genes function as regulators of development and pattern formation in early embryogenesis. We have obtained a novel forkhead domain transcription factor, MFH-1 (Mesenchyme Forkhead-1) and preliminary studies suggest that it is expressed in condensing metanephric mesenchyme at a critical stage in the mesenchymal-epithelial transition. Nothing is known of the structure/function or role in kidney development of MFH-1. In this proposal, we will perform a comprehensive developmental and biochemical analysis for MFH-I specifically, we will l) determine the spatio-temporal, cell-type-specific expression patterns in murine development and in the kidney organ culture system in vitro using high resolution in-situ hybridization and immunohistochemistry, 2) isolate and characterize the genomic clones/ promotor regions and localize genetic elements required for kidney-cell specific expression, 3) isolate the DNA binding sites recognized by MFH-1 protein and utilize this information to search for potential target genes, and 4) determine the biological consequences of ablating MFH-1 expression using antisense oligonucleotides in the kidney organ culture system and in established cell lines. This analysis should provide a comprehensive look at a novel forkhead domain transcription factor in murine kidney organogenesis and provide new insights into the regulation of differentiation during the nephrogenic process.
| 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 |
Showing the most recent 10 out of 220 publications
