RhoA Regulation of Cardiomyocyte Differentiation

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...

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Main Authors: Mari Kaarbø, Denis I. Crane, Wayne G. Murrell
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1155/2013/491546
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author Mari Kaarbø
Denis I. Crane
Wayne G. Murrell
author_facet Mari Kaarbø
Denis I. Crane
Wayne G. Murrell
author_sort Mari Kaarbø
collection DOAJ
description 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.
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spelling doaj-art-2256c55771594abeb4ee03a2364f433b2025-02-03T06:00:19ZengWileyThe Scientific World Journal1537-744X2013-01-01201310.1155/2013/491546491546RhoA Regulation of Cardiomyocyte DifferentiationMari Kaarbø0Denis I. Crane1Wayne G. Murrell2Department of Microbiology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0454 Oslo, NorwayCell Biology, Eskitis Institute for Cell and Molecular Therapies, and School of Biomolecular and Biomedical Science, Griffith University, Nathan, QD 4111, AustraliaVilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, 0454 Oslo, NorwayEarlier 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.http://dx.doi.org/10.1155/2013/491546
spellingShingle Mari Kaarbø
Denis I. Crane
Wayne G. Murrell
RhoA Regulation of Cardiomyocyte Differentiation
The Scientific World Journal
title RhoA Regulation of Cardiomyocyte Differentiation
title_full RhoA Regulation of Cardiomyocyte Differentiation
title_fullStr RhoA Regulation of Cardiomyocyte Differentiation
title_full_unstemmed RhoA Regulation of Cardiomyocyte Differentiation
title_short RhoA Regulation of Cardiomyocyte Differentiation
title_sort rhoa regulation of cardiomyocyte differentiation
url http://dx.doi.org/10.1155/2013/491546
work_keys_str_mv AT marikaarbø rhoaregulationofcardiomyocytedifferentiation
AT denisicrane rhoaregulationofcardiomyocytedifferentiation
AT waynegmurrell rhoaregulationofcardiomyocytedifferentiation