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
AUTHORS (14)
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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CITATIONS (105)
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