DETERMINATION AND DIVERSIFICATION OF CARDIAC MYOBLASTS

1%的人心脏发育不正常 出生。尽管如此，控制细胞和分子的基本控制 心肌细胞的发生尚不清楚。计划的长期目标 研究是为了了解细胞和分子机制 直接测定心肌成肌细胞及其晚期 分化为房室和传导系统的肌细胞。 具体来说，我们的目标是：1)鉴定细胞和分子 心源性测定的基础：20测定细胞和 心肌细胞多样化的分子基础；30识别基因 直接引发心脏疾病的承诺。新开发的微型培养系统 允许在体外进行心源性分化的克隆分析 将被用来确定促进 心肌成肌细胞的测定和多样化。5-氮胞苷 治疗和DNA导入将被用来“挽救”分化 阻断心肌成肌细胞，以努力鉴定和分离基因 直接进行心源性测定。单抗和cDNA 对于肌球蛋白重链将被用来监测细胞和 异质性心肌细胞群的分子机制 都是生成的。综上所述，希望这些研究将有助于 我们对最初的决定和后来的基本理解 心肌细胞的多样化在功能上的形成 心肌。来自拟议研究的数据将提供基本的 关于细胞和分子机制的信息 异质的心肌细胞群体，为分析奠定了基础 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.