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

163 Citations (Scopus)

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

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Endocardium
Morphogenesis
Chromatin
Secreted Matrix Metalloproteinases
Chromatin Assembly and Disassembly
Cardiomyopathies
Heart Ventricles
Embryonic Development
Vertebrates
Growth
Tissue
Proteins
Chemical analysis

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Endocardial Brg1 Represses ADAMTS1 to Maintain the Microenvironment for Myocardial Morphogenesis. / Stankunas, Kryn; Hang, Calvin T.; Tsun, Zhi Yang; Chen, Hanying; Lee, Nathan V.; Wu, Jiang I.; Shang, Ching; Bayle, J. Henri; Shou, Weinian; Iruela-Arispe, M. Luisa; Chang, Ching-Pin.

In: Developmental Cell, Vol. 14, No. 2, 12.02.2008, p. 298-311.

Research output: Contribution to journalArticle

Stankunas, K, Hang, CT, Tsun, ZY, Chen, H, Lee, NV, Wu, JI, Shang, C, Bayle, JH, Shou, W, Iruela-Arispe, ML & Chang, C-P 2008, 'Endocardial Brg1 Represses ADAMTS1 to Maintain the Microenvironment for Myocardial Morphogenesis', Developmental Cell, vol. 14, no. 2, pp. 298-311. https://doi.org/10.1016/j.devcel.2007.11.018
Stankunas, Kryn ; Hang, Calvin T. ; Tsun, Zhi Yang ; Chen, Hanying ; Lee, Nathan V. ; Wu, Jiang I. ; Shang, Ching ; Bayle, J. Henri ; Shou, Weinian ; Iruela-Arispe, M. Luisa ; Chang, Ching-Pin. / Endocardial Brg1 Represses ADAMTS1 to Maintain the Microenvironment for Myocardial Morphogenesis. In: Developmental Cell. 2008 ; Vol. 14, No. 2. pp. 298-311.
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