Prox1 maintains muscle structure and growth in the developing heart
Date
2009
Authors
Risebro, C.
Searles, R.
Melville, A.
Ehler, E.
Jina, N.
Shah, S.
Pallas, J.
Hubank, M.
Dillard, M.
Harvey, N.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Development, 2009; 136(3):495-505
Statement of Responsibility
Catherine A. Risebro, Richelle G. Searles, Athalie A. D. Melville, Elisabeth Ehler, Nipurna Jina, Sonia Shah, Jacky Pallas, Mike Hubank, Miriam Dillard, Natasha L. Harvey, Robert J. Schwartz, Kenneth R. Chien, Guillermo Oliver and Paul R. Riley
Conference Name
Abstract
Impaired cardiac muscle growth and aberrant myocyte arrangement underlie congenital heart disease and cardiomyopathy. We show that cardiac-specific inactivation of the murine homeobox transcription factor Prox1 results in the disruption of expression and localisation of sarcomeric proteins, gross myofibril disarray and growth-retarded hearts. Furthermore, we demonstrate that Prox1 is required for direct transcriptional regulation of the genes encoding the structural proteins -actinin, N-RAP and zyxin, which collectively function to maintain an actin--actinin interaction as the fundamental association of the sarcomere. Aspects of abnormal heart development and the manifestation of a subset of muscular-based disease have previously been attributed to mutations in key structural proteins. Our study reveals an essential requirement for direct transcriptional regulation of sarcomere integrity, in the context of enabling foetal cardiomyocyte hypertrophy, maintenance of contractile function and progression towards inherited or acquired myopathic disease.