Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis
Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis
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DOI：
10.1016/j.devcel.2007.11.018
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发表时间：
2008-02-01
影响因子：
11.8
通讯作者：
Chang, Ching-Pin
中科院分区：
文献类型：
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作者：
Stankunas, Kryn;Hang, Calvin T.;Chang, Ching-Pin
发育中的心肌细胞对来自心内膜层的信号做出反应，形成小梁网络，这是脊椎动物心脏心室的特征。在人类中，异常的心肌小梁会导致特定的心肌疾病，但对小梁的发育知之甚少。我们发现，小梁形成需要一种染色质重塑蛋白BRG1来抑制位于发育中的小梁之上的心内膜中ADAMTS1的表达。抑制ADAMTS1，一种分泌的基质金属蛋白酶，允许在心脏凝胶中建立支持小梁生长的细胞外环境。在胚胎发育的后期，ADAMTS1在心内膜中开始表达，以降解心脏凝胶并防止过度的小梁形成。因此，心肌形态发生所必需的心脏凝胶的组成由ADAMTS1及其基于染色质的转录调控动态控制。中间微环境的改变提供了一种机制，通过该机制，一个组织层内的染色质调节协调相邻层的形态发生。
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.