NDLI: A Dual Role of the GTPase Rac in Cardiac Differentiation of Stem Cells

Content Provider	PubMed Central
Author	Michel, Pucéat Pierre, Travo Quinn, Mark T. Fort, Philipe
Editor	Richard, Assoian
Copyright Year	2003
Abstract	The function of the GTPase Rac1, a molecular switch transducing intracellular signals from growth factors, in differentiation of a specific cell type during early embryogenesis has not been investigated. To address the question, we used embryonic stem (ES) cells differentiated into cardiomyocytes, a model that faithfully recapitulates early stages of cardiogenesis. Overexpression in ES cells of a constitutively active Rac (RacV12) but not of an active mutant (RacL61D38), which does not activate the NADPH oxydase generating ROS, prevented MEF2C expression and severely compromised cardiac cell differentiation. This resulted in poor expression of ventricular myosin light chain 2 (MLC2v) and its lack of insertion into sarcomeres. Thus ES-derived cardiomyocytes featured impaired myofibrillogenesis and contractility. Overexpression of MEF2C or addition of catalase in the culture medium rescued the phenotype of racV12 cells. In contrast, RacV12 specifically expressed in ES-derived ventricular cells improved the propensity of cardioblasts to differentiate into beating cardiomyocytes. This was attributed to both a facilitation of myofibrillogenesis and a prolongation in their proliferation. The dominant negative mutant RacN17 early or lately expressed in ES-derived cells prevented myofibrillogenesis and in turn beating of cardiomyocytes. We thus suggest a stage-dependent function of the GTPase during early embryogenesis.
Related Links	http://dx.doi.org/10.1091/mbc.e02-09-0562
Ending Page	2792
Page Count	12
Starting Page	2781
File Format	PDF
ISSN	10591524
Journal	Molecular Biology of the Cell
Issue Number	7
Volume Number	14
Language	English
Publisher	The American Society for Cell Biology
Publisher Date	2003-04-01
Access Restriction	Open
Rights Holder	The American Society for Cell Biology
Subject Keyword	Cell Biology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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