Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis.
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.
Stankunas
Kryn
K
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hang
Calvin T
CT
Tsun
Zhi-Yang
ZY
Chen
Hanying
H
Lee
Nathan V
NV
Wu
Jiang I
JI
Shang
Ching
C
Bayle
J Henri
JH
Shou
Weinian
W
Iruela-Arispe
M Luisa
ML
Chang
Ching-Pin
CP
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000818:Animals; D002460:Cell Line; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004699:Endocardium / Q000378:metabolism*; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis; D005109:Extracellular Matrix / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006352:Heart Ventricles / Q000196:embryology; D006801:Humans; D051379:Mice; D009024:Morphogenesis; D018919:Neovascularization, Physiologic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015017:Yolk Sac / Q000098:blood supply
D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486323:Adamts1 protein, mouse; C513194:Smarca4 protein, mouse; D004265:DNA Helicases