Endocardial Brg1 Represses ADAMTS1 to Maintain the Microenvironment for Myocardial Morphogenesis

Kryn Stankunas, Calvin T. Hang, Zhi Yang Tsun, Hanying Chen, Nathan V. Lee, Jiang I. Wu, Ching Shang, J. Henri Bayle, Weinian Shou, M. Luisa Iruela-Arispe, Ching Pin Chang

Research output: Contribution to journalArticle

170 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)298-311
Number of pages14
JournalDevelopmental cell
Volume14
Issue number2
DOIs
StatePublished - Feb 12 2008

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Stankunas, K., Hang, C. T., Tsun, Z. Y., Chen, H., Lee, N. V., Wu, J. I., Shang, C., Bayle, J. H., Shou, W., Iruela-Arispe, M. L., & Chang, C. P. (2008). Endocardial Brg1 Represses ADAMTS1 to Maintain the Microenvironment for Myocardial Morphogenesis. Developmental cell, 14(2), 298-311. https://doi.org/10.1016/j.devcel.2007.11.018