Prox1 maintains muscle structure and growth in the developing heart

Heart Defects, Congenital Sarcomeres 570 N-RAP (Nrap) Mouse Myopathy 610 Muscle Proteins Mice, Transgenic zyxin Heart development hypertrophy mouse 1309 Developmental Biology Mice 03 medical and health sciences Prox1 Metalloproteins 1312 Molecular Biology myocardium Animals Actinin Homeodomain Proteins 0303 health sciences Myocardium Tumor Suppressor Proteins Sarcomere Gene Expression Regulation, Developmental Heart Hypertrophy heart development Embryo, Mammalian Myocardial Contraction Zyxin 3. Good health sarcomere myopathy
DOI: 10.1242/dev.030007 Publication Date: 2008-12-18T01:25:04Z
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 α-actinin, N-RAP and zyxin, which collectively function to maintain an actin-α-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.
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