The broad objective of this work is to understand the basis of formation of the ventricular chamber of the heart. This project specifically considers two distinct processes: how do cardiac muscle cells (cardiomyocytes) expand in number (proliferate), and how do coronary blood vessels form. These processes are related by virtue of being controlled by signals from the outer layer of the heart, a cell type called the epicardium. This project seeks to understand the role and mechanistic basis of these signals, primarily utilizing genetically engineered mice, explanted embryonic mouse tissue, and tissue culture cells to conduct this research.

Public Health Relevance

Heart disease is the leading cause of death in the Western world, and is pernicious because damaged adult heart muscle is mostly not able to repair itself and regenerate. Two critical processes that would be needed for successful regeneration include the growth of cardiac muscle and the reformation of a functional vascular supply. It is widely felt that strategies based on normal processes that occur during embryonic heart development will offer the greatest likelihood for successful treatment of adult heart disease. The primary focus of this project is to address how cardiac muscle and coronary vascular formation occur in the embryo.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Schramm, Charlene A
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University of Southern California
Anatomy/Cell Biology
Schools of Medicine
Los Angeles
United States
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Cavallero, Susana; Shen, Hua; Yi, Christopher et al. (2015) CXCL12 Signaling Is Essential for Maturation of the Ventricular Coronary Endothelial Plexus and Establishment of Functional Coronary Circulation. Dev Cell 33:469-77
Shen, Hua; Cavallero, Susana; Estrada, Kristine D et al. (2015) Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion. Cardiovasc Res 105:271-8
Yamaguchi, Yukiko; Cavallero, Susana; Patterson, Michaela et al. (2015) Adipogenesis and epicardial adipose tissue: a novel fate of the epicardium induced by mesenchymal transformation and PPAR? activation. Proc Natl Acad Sci U S A 112:2070-5
Cambier, Linda; Plate, Markus; Sucov, Henry M et al. (2014) Nkx2-5 regulates cardiac growth through modulation of Wnt signaling by R-spondin3. Development 141:2959-71
Engelhard, Caitlin; Sarsfield, Sarah; Merte, Janna et al. (2013) MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons. Elife 2:e01160
Huang, Ying; Harrison, Michael R; Osorio, Arthela et al. (2013) Igf Signaling is Required for Cardiomyocyte Proliferation during Zebrafish Heart Development and Regeneration. PLoS One 8:e67266
Li, Peng; Cavallero, Susana; Gu, Ying et al. (2011) IGF signaling directs ventricular cardiomyocyte proliferation during embryonic heart development. Development 138:1795-805
Brade, Thomas; Kumar, Sandeep; Cunningham, Thomas J et al. (2011) Retinoic acid stimulates myocardial expansion by induction of hepatic erythropoietin which activates epicardial Igf2. Development 138:139-48
Sucov, Henry M; Gu, Ying; Thomas, Simmy et al. (2009) Epicardial control of myocardial proliferation and morphogenesis. Pediatr Cardiol 30:617-25
Kang, Jione; Gu, Ying; Li, Peng et al. (2008) PDGF-A as an epicardial mitogen during heart development. Dev Dyn 237:692-701