This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. During embryonic development the early vascular plexus forms through the process called Vasculogenesis, In response to growth factors, endothelial precursor cells differentiate to endothelial cells and migrate to form new blood vessels. The early vascular plexus is then extended through angiogenesis in which new vessels are formed from existing vessels. In adults, angiogenesis is also involved in multiple physiological and pathological (e.g. tumor angiogenesis) conditions. VEGFR family of receptor tyrosine kinases (RTKs) are crucial for vascular development during embryogenesis as well as physiological and pathological angiogenesis in adults.Multiple transcription factors, including ETS and hypoxia inducible factors (HIFs)have been implicated in establishing endothelial cell-specific gene expression. So, we hypothesize that an angiogenic signal-ETS1/HIF-2alpha axis regulates transcription of VEGFRs and other key genes in vascular endothelium. In this study, using gain-in- and loss-of-function approaches with mouse embryonic stem cell (ES cell) differentiation system, we will test whether ETS1 and HIF-2alpha regulate VEGFR expression during endothelial differentiation. Analysis will be performed with ES cells, ES cell-derived endothelial progenitor cells and endothelial cells to test the hypothesis that during endothelial differentiation VEGFR1 and VEGFR2 chromatin domains are regulated by ETS1 and HIF-2alpha. In addition, we will determine the importance of the functional co-operation of ETS1 and HIF-2alpha during vascular development by generating mice lacking both ETS1 and HIF-2alpha. Angiogenesis is critical for certain pathological disorders including tumor growth/metastasis. Information gleaned from these studies will contribute to our understanding of the molecular mechanisms of angiogenesis and hopefully will lead to novel therapeutic modalities.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR024214-05
Application #
8360684
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2011-07-01
Project End
2012-08-31
Budget Start
2011-07-01
Budget End
2012-12-30
Support Year
5
Fiscal Year
2011
Total Cost
$216,633
Indirect Cost
Name
University of Kansas
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Pohler, Ky G; Green, Jonathan A; Moley, Laura A et al. (2017) Circulating microRNA as candidates for early embryonic viability in cattle. Mol Reprod Dev 84:731-743
Rogers, Robert S; Tungtur, Sudheer; Tanaka, Tomohiro et al. (2017) Impaired Mitophagy Plays a Role in Denervation of Neuromuscular Junctions in ALS Mice. Front Neurosci 11:473
Navakanitworakul, Raphatphorn; Hung, Wei-Ting; Gunewardena, Sumedha et al. (2016) Characterization and Small RNA Content of Extracellular Vesicles in Follicular Fluid of Developing Bovine Antral Follicles. Sci Rep 6:25486
Aleksandrova, Anastasiia; Czirok, Andras; Kosa, Edina et al. (2015) The endoderm and myocardium join forces to drive early heart tube assembly. Dev Biol 404:40-54
Nishimune, Hiroshi; Stanford, John A; Mori, Yasuo (2014) Role of exercise in maintaining the integrity of the neuromuscular junction. Muscle Nerve 49:315-24
Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina et al. (2014) Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice. Proc Natl Acad Sci U S A 111:5735-40
Zhang, Yu-Kun Jennifer; Lu, Hong; Klaassen, Curtis D (2013) Expression of human CAR splicing variants in BAC-transgenic mice. Toxicol Sci 132:142-50
Elsarraj, Hanan S; Hong, Yan; Valdez, Kelli et al. (2013) A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance. J Cell Sci 126:2446-58
Galvin-Burgess, Katherine E; Travis, Emily D; Pierson, Kelsey E et al. (2013) TGF-?-superfamily signaling regulates embryonic stem cell heterogeneity: self-renewal as a dynamic and regulated equilibrium. Stem Cells 31:48-58
Wouthuyzen-Bakker, Marjan; Bijvelds, Marcel J C; de Jonge, Hugo R et al. (2012) Effect of antibiotic treatment on fat absorption in mice with cystic fibrosis. Pediatr Res 71:4-12

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