DETERMINATION AND DIVERSIFICATION OF CARDIAC MYOBLASTS

心脏发育异常发生在百分之一的人身上。 出生尽管如此，基本的细胞和分子控制， 心肌发生是未知的。项目的长期目标 研究是为了了解细胞和分子机制， 指导心肌成肌细胞的测定及其后期的研究 分化成心房、心室和传导系统肌细胞。 具体来说，我们的目标是：1）识别细胞和分子 心源性测定的基础：20，以确定细胞和 心肌细胞多样化的分子基础; 30个识别基因 这直接心源性承诺。新开发的微培养系统 其允许体外心源性分化的克隆分析 将被用来确定细胞类型，促进 心肌成肌细胞的确定和多样化。5-氮杂胞苷 治疗和DNA转染将用于“拯救”分化 阻断了心肌成肌细胞， 其指导心源性决定。单克隆抗体和cDNA 肌球蛋白重链将用于监测细胞和 异质性心肌细胞群的分子机制 产生的。总之，希望这些研究将有助于 我们对最初确定的基本认识， 心肌细胞的多样化在形成一个功能 心肌研究数据将提供基础 关于细胞和分子机制的信息， 异质群体的肌细胞，并奠定了基础， 心脏发育异常

Abnormal development of the heart occurs in one percent of all human births. Still, the basic cellular and molecular controls which govern cardiac myogenesis are unknown. The long term goals of the projected research are to understand the cellular and molecular mechanisms which direct the determination of cardiac myoblasts and their later diversification into atrial, ventricular and conduction system myocytes. Specifically, our aims are: 1) to identify the cellular and molecular bases of cardiogenic determination: 20 to determine the cellular and molecular bases of cardiac myocyte diversification; 30 to identify genes which direct cardiogenic commitment. Newly developed microculture systems which permit the clonal analysis of cardiogenic differentiation in vitro will be employed to determine the cell types which promote the determination and diversification of cardiac myoblasts. 5-azacytidine treatment and DNA transfection will be used to "rescue" differentiation blocked cardiac myoblasts in an effort to identify and isolate the genes which direct cardiogenic determination. Monoclonal antibodies and cDNAs for the myosin heavy chain will be used to monitor the cellular and molecular mechanisms by which heterogeneous cardiac myocyte populations are generated. Taken together, it is hoped that these studies will aid in our basic understanding of the initial determination and later diversification of cardiac myocytes in the formation of a functional myocardium. Data from the proposed research will provide basic information concerning the cellular and molecular mechanisms by which heterogeneous populations of myocytes and lay the groundwork for analysis of abnormal heart development.