Heart development involves the generation and interaction of diverse cell types to form a functional organ. Myocytes, endocardium, fibroblasts, epicardium, vascular endothelium and smooth muscle are the primary cell types that comprise the heart. The pro-epicardial organ is the source of many of these cells. It is a transitory embryonic structure whose progeny form, amongst other structures, the epicardium and intracardiac arteries including the coronary arteries.. Thus, an understanding of the role of the pro-epicardial organ and its progeny is essential for an understanding of heart development. We have isolated novel protein, Bves, that is expressed in most, if not cells of the pro-epicardial organ, migrating epicardial, delaminated freely migratory mesenchyme and coronary vascular smooth muscle cells. In addition, the subcellular localization of Bves undergoes a dramatic change with differentiation of this cell lineage. Our current data suggests that Bves is a protein that may play a role in cell adhesion during coronary vessel development.
Our aims are to determine whether Bves is an integrated membrane (Aim ), to identify domains that regulate Bves function in vitro and during organogenesis (Aim 2) and to determine how loss of Bves function potentially alters morphogenesis (Aim 3). Taken together these aims will determine the function(s) of Bves, its role in the generation of coronary vessels and basic insight into coronary vessel biology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL067105-04
Application #
6893310
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2004-05-01
Project End
2006-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
4
Fiscal Year
2004
Total Cost
$329,583
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Criswell, Tracy L; Dumont, Nancy; Barnett, Joey V et al. (2008) Knockdown of the transforming growth factor-beta type III receptor impairs motility and invasion of metastatic cancer cells. Cancer Res 68:7304-12
Hayashi, Hisaki; Kume, Tsutomu (2008) Foxc transcription factors directly regulate Dll4 and Hey2 expression by interacting with the VEGF-Notch signaling pathways in endothelial cells. PLoS One 3:e2401
Hayashi, Hisaki; Sano, Hideto; Seo, Seungwoon et al. (2008) The Foxc2 transcription factor regulates angiogenesis via induction of integrin beta3 expression. J Biol Chem 283:23791-800
Hayashi, Hisaki; Kume, Tsutomu (2008) Forkhead transcription factors regulate expression of the chemokine receptor CXCR4 in endothelial cells and CXCL12-induced cell migration. Biochem Biophys Res Commun 367:584-9
Austin, Anita F; Compton, Leigh A; Love, Joseph D et al. (2008) Primary and immortalized mouse epicardial cells undergo differentiation in response to TGFbeta. Dev Dyn 237:366-76
Compton, Leigh A; Potash, Dru A; Brown, Christopher B et al. (2007) Coronary vessel development is dependent on the type III transforming growth factor beta receptor. Circ Res 101:784-91
Smith, Travis K; Bader, David M (2006) Characterization of Bves expression during mouse development using newly generated immunoreagents. Dev Dyn 235:1701-8
Compton, Leigh A; Potash, Dru A; Mundell, Nathan A et al. (2006) Transforming growth factor-beta induces loss of epithelial character and smooth muscle cell differentiation in epicardial cells. Dev Dyn 235:82-93
Seo, Seungwoon; Fujita, Hideo; Nakano, Atsushi et al. (2006) The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev Biol 294:458-70
Olivey, Harold E; Mundell, Nathan A; Austin, Anita F et al. (2006) Transforming growth factor-beta stimulates epithelial-mesenchymal transformation in the proepicardium. Dev Dyn 235:50-9

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