1. Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis.
- Author
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Stankunas K, Hang CT, Tsun ZY, Chen H, Lee NV, Wu JI, Shang C, Bayle JH, Shou W, Iruela-Arispe ML, and Chang CP
- Subjects
- ADAM Proteins genetics, ADAMTS1 Protein, Animals, Cell Line, DNA Helicases genetics, Embryo, Mammalian cytology, Embryo, Mammalian metabolism, Endothelium cytology, Endothelium metabolism, Erythropoiesis, Extracellular Matrix metabolism, Gene Expression Regulation, Developmental, Heart Ventricles embryology, Humans, Mice, Neovascularization, Physiologic, Nuclear Proteins genetics, Promoter Regions, Genetic genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Repressor Proteins genetics, Repressor Proteins metabolism, Transcription Factors genetics, Yolk Sac blood supply, ADAM Proteins metabolism, DNA Helicases metabolism, Endocardium metabolism, Heart embryology, Morphogenesis, Nuclear Proteins metabolism, Transcription Factors metabolism
- Abstract
Developing myocardial cells respond to signals from the endocardial layer to form a network of trabeculae that characterize the ventricles of the vertebrate heart. Abnormal myocardial trabeculation results in specific cardiomyopathies in humans and yet trabecular development is poorly understood. We show that trabeculation requires Brg1, a chromatin remodeling protein, to repress ADAMTS1 expression in the endocardium that overlies the developing trabeculae. Repression of ADAMTS1, a secreted matrix metalloproteinase, allows the establishment of an extracellular environment in the cardiac jelly that supports trabecular growth. Later during embryogenesis, ADAMTS1 expression initiates in the endocardium to degrade the cardiac jelly and prevent excessive trabeculation. Thus, the composition of cardiac jelly essential for myocardial morphogenesis is dynamically controlled by ADAMTS1 and its chromatin-based transcriptional regulation. Modification of the intervening microenvironment provides a mechanism by which chromatin regulation within one tissue layer coordinates the morphogenesis of an adjacent layer.
- Published
- 2008
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