Desmin stimulates differentiation of cardiomyocytes and up-regulation of brachyury and nkx2.5.
Desmin contributes to structural integrity and function of the myocardium but its function seems to be redundant in early cardiomyogenesis in the desmin null mouse model. To test the hypothesis that desmin also plays a supportive role in cardiomyogenic commitment and early differentiation of cardiomyocytes we investigated cardiomyogenesis in embryoid bodies expressing different desmin alleles. Constitutive expression of desmin and increased synthesis during mesoderm formation led to the up-regulation of brachyury and nkx2.5 genes, accelerated early cardiomyogenesis and resulted in the development of large, proliferating, highly interconnected, and synchronously beating cardiomyocyte clusters, whereas desmin null cardiomyocytes featured an opposite phenotype. In contrast, constitutive expression of amino-terminally truncated desmin(Delta1-48) interfered with the beginning of cardiomyogenesis, caused down-regulation of mesodermal and myocardial transcription factors, and hampered myofibrillogenesis and survival of cardiomyocytes. These results provide first evidence that a type III intermediate filament protein takes part in regulating the differentiation of mesoderm to cardiomyocytes at the very beginning of cardiomyogenesis.
Hofner
Manuela
M
Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Dr. Bohrgasse 9, A1030 Vienna, Austria.
Höllrigl
Alexandra
A
Puz
Sonja
S
Stary
Martina
M
Weitzer
Georg
G
D000818:Animals; D002449:Cell Aggregation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003893:Desmin / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005326:Fetal Proteins / Q000096:biosynthesis* / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics*; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*; D000098908:Brachyury Protein
D003893:Desmin; D005326:Fetal Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C484469:Nkx2-5 protein, mouse