MOLECULAR GENETICS OF CARDIAC CELL DIFFERENTIATION

描述(改编自申请人的摘要)：申请人的 长期目标是了解心肌细胞的分子机制 差异化。斑马鱼将作为模型系统进行研究 心脏编队。在所有脊椎动物中，早期的心管是由 只有两种细胞类型，外心肌和内心内膜 细胞。在这项提案中，申请人的目的是调查其来源 心内膜细胞的分化及其在心脏中的作用 队形。通过大规模的诱变筛选，申请人已经 已经确定了几个特定影响 早期心管的形成；特别是一种，闭合体， 选择性地删除心内膜细胞。在克洛奇突变体中， 在没有心内膜的情况下形成心肌管，但 畸形，表现为收缩减少。建议的目标是： (1)确定迁徙路径并分析其谱系 心内膜细胞；(2)为了进一步鉴定闭锁突变， 识别更多的克隆氏等位基因，绘制克隆氏突变的基因图谱， 用定位克隆的方法分离Cloche基因，并鉴定其他 心内膜细胞分化途径的组成部分；和(3) 心内膜细胞在心肌细胞成熟中的作用 和功能。

DESCRIPTION (adapted from the applicant's abstract): The applicant's long-term goal is to understand molecular mechanisms of cardiac cell differentiation. The zebrafish will be used as a model system to study heart formation. In all vertebrates, the early heart tube is composed of only two cell types, the outer myocardial and inner endocardial cells. In this proposal the applicant aims to investigate the origin and differentiation of the endocardial cells and their role in heart formation. Through large scale mutagenesis screens, the applicant has already identified several mutations that specifically affect the formation of the early heart tube; one in particular, cloche, selectively deletes the endocardial cells. In cloche mutants, the myocardial tube forms in the absence of the endocardium but is dysmorphic and exhibits a reduced contraction. The proposed aims are: (1) to determine the migration pathways and analyze the lineage of endocardial cells; (2) to further characterize the cloche mutation, identify additional cloche alleles, map the cloche mutation genetically, isolate the cloche gene by positional cloning, and identify other components in the pathway of endocardial cell differentiation; and (3) to determine the role of endocardial cells in myocardial cell maturation and function.