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The Scientific World Journal
Volume 2013 (2013), Article ID 491546, 12 pages
http://dx.doi.org/10.1155/2013/491546
Research Article

RhoA Regulation of Cardiomyocyte Differentiation

1Department of Microbiology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0454 Oslo, Norway
2Cell Biology, Eskitis Institute for Cell and Molecular Therapies, and School of Biomolecular and Biomedical Science, Griffith University, Nathan, QD 4111, Australia
3Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, 0454 Oslo, Norway

Received 17 April 2013; Accepted 14 May 2013

Academic Editors: A. Aronheim, A. S. Balajee, and G. Min

Copyright © 2013 Mari Kaarbø et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Earlier findings from our laboratory implicated RhoA in heart developmental processes. To investigate factors that potentially regulate RhoA expression, RhoA gene organisation and promoter activity were analysed. Comparative analysis indicated strict conservation of both gene organisation and coding sequence of the chick, mouse, and human RhoA genes. Bioinformatics analysis of the derived promoter region of mouse RhoA identified putative consensus sequence binding sites for several transcription factors involved in heart formation and organogenesis generally. Using luciferase reporter assays, RhoA promoter activity was shown to increase in mouse-derived P19CL6 cells that were induced to differentiate into cardiomyocytes. Overexpression of a dominant negative mutant of mouse RhoA (mRhoAN19) blocked this cardiomyocyte differentiation of P19CL6 cells and led to the accumulation of the cardiac transcription factors SRF and GATA4 and the early cardiac marker cardiac α-actin. Taken together, these findings indicate a fundamental role for RhoA in the differentiation of cardiomyocytes.