We have shown that all coronary progenitors arise exclusively from the epicardial anlagen termed the _roepicardium (PE). It is currently unknown, however, how and when the various coronary vascular cell rpes, including endothelial cells, are induced and what mechanisms govern their entry into the heart. Our preliminary data show that PE formation occurs in the mesoderm immediately posterior to the presumptive heart tube and in close proximity to the underlying endoderm-derived liver primordium. A subpopulation of PE cells express differentiation markers for either endothelial or smooth muscle cells. Furthermore, migration of PE cells can be activated by a myocardium-derived paracrine signal(s). Finally, several BMP members, expressed by the myocardium, can activate migration of embryonic endothelial cells. These data lead to the hypothesis that coronary progenitors, including endothelial cells, are induced and recruited to the heart via a three-step mechanism: 1) specification of PE cells within the mesoderm, 2) induction of a vascular cell fate within the PE, and 3) directional migration of the coronary progenitors to the heart. We will test these three specific hypotheses by: determining a novel inductive role of the liver primordium in the PE fate specification (Aim 1);identifying the differentiation potential of individual PE cells (Aim 2);and testing a chemoattractant role of myocardium-derived BMP signaling in targeted migration of coronary progenitors to the heart (Aim 3). The studies proposed here will identify the regulators of three critical steps in establishing coronary arterial vasculature and build a foundation for rational therapeutics of coronary disorders in adults.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL078921-06
Application #
7534808
Study Section
Special Emphasis Panel (ZRG1-CDD (01))
Program Officer
Schramm, Charlene A
Project Start
2004-12-15
Project End
2009-11-30
Budget Start
2008-12-01
Budget End
2009-11-30
Support Year
6
Fiscal Year
2009
Total Cost
$366,235
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bressan, Michael; Henley, Trevor; Louie, Jonathan D et al. (2018) Dynamic Cellular Integration Drives Functional Assembly of the Heart's Pacemaker Complex. Cell Rep 23:2283-2291
Bressan, Michael; Mikawa, Takashi (2015) Avians as a model system of vascular development. Methods Mol Biol 1214:225-42
Bressan, Michael; Yang, PoAn Brian; Louie, Jonathan D et al. (2014) Reciprocal myocardial-endocardial interactions pattern the delay in atrioventricular junction conduction. Development 141:4149-57
Bressan, Michael C; Louie, Jonathan D; Mikawa, Takashi (2014) Hemodynamic forces regulate developmental patterning of atrial conduction. PLoS One 9:e115207
Garriock, Robert J; Czeisler, Catherine; Ishii, Yasuo et al. (2010) An anteroposterior wave of vascular inhibitor downregulation signals aortae fusion along the embryonic midline axis. Development 137:3697-706
Oda-Ishii, Izumi; Ishii, Yasuo; Mikawa, Takashi (2010) Eph regulates dorsoventral asymmetry of the notochord plate and convergent extension-mediated notochord formation. PLoS One 5:e13689
Ishii, Yasuo; Garriock, Robert J; Navetta, Alicia M et al. (2010) BMP signals promote proepicardial protrusion necessary for recruitment of coronary vessel and epicardial progenitors to the heart. Dev Cell 19:307-16
Bressan, Michael; Davis, Patricia; Timmer, John et al. (2009) Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation. Dev Biol 326:101-11
Ishii, Yasuo; Langberg, Jonathan; Rosborough, Kelley et al. (2009) Endothelial cell lineages of the heart. Cell Tissue Res 335:67-73
Ishii, Yasuo; Weinberg, Kerry; Oda-Ishii, Izumi et al. (2009) Morphogenesis and cytodifferentiation of the avian retinal pigmented epithelium require downregulation of Group B1 Sox genes. Development 136:2579-89

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