The proposed studies will examine the role of the integrin family of exctrcellular matrix (ECM) receptors in signalling between the ECM and the cell. While these receptors have been known for several years, their precise function(s) have only been theoretical. The proposed studies will address two hypotheses: 1) that the beta1 integrins are important signalling molecules with influence cardiac myofibrillogenesis and the induction of genes which define the hypertrophic myocyte phenotype; and 2) that the cytoplasmic domain of the beta1 provides a means to modulate ventricular chamber formation during cardiac development. To address these hypotheses 3 specific aims will examine: 1) the role of the beta1 cytoplasmic domain in signalling myocytes during cellular organization in the basal state, and during re-organization of the cell during stimulation of the spread/hypertrophic phenotype, in vitro; 2) how beta1 integrin cytoplasmic domain signaling influences normal cardiac development during early Murine cardiogenesis using an ex vivo murine embryo culture system and an ES/embryoid body system; and 3) evaluate the role of the beta1 integrin in cardiac chamber and outflow tract formation in vivo by using cardiac-specific expression of a dominant negative beta1 negative mutant transgenic mice.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057872-05
Application #
6184098
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Wang, Lan-Hsiang
Project Start
1996-08-01
Project End
2001-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
5
Fiscal Year
2000
Total Cost
$278,927
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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