Genetic regulation of cell fate in the Drosophila heart

描述（由申请人提供）：本申请的长期目标是使用果蝇系统来定义心脏发育的基本分子机制。果蝇有一个原始的心管，称为背血管，它由许多独特的细胞类型组成，每一种细胞类型在成熟的器官中都有特定的功能。虽然关于心脏细胞最初是如何被指定的了解很多，但关于心脏中胚层中的单个细胞如何获得独特的命运，还有很多需要了解的。我们将使用遗传学和分子生物学来识别背血管中表达受限的基因的转录调节因子，并了解独特的细胞类型如何在心脏中胚层中产生和分化。现在有令人信服的证据表明，心脏规范和分化的分子机制在进化过程中是高度保守的，我们相信这也将被证明是具有心脏谱系的独特细胞类型获得的情况，正如本文所提出的那样。因此，我们的研究将直接关系到对包括人类在内的脊椎动物心脏发育的理解。此外，由于许多先天性心脏缺陷最近被证明是由心脏转录因子的突变引起的，我们关于心脏细胞命运的转录控制的研究可能为理解脊椎动物心脏病的机制提供关键的基础信息。

DESCRIPTION (provided by applicant): The long-term goal of this application is to use the Drosophila system to define basic molecular mechanisms in heart development. Drosophila have a primitive cardiac tube termed the dorsal vessel which comprises a number of unique cell types, each of which perform specific functions in the mature organ. While much is known concerning how the heart cells are initially specified there is still much to learn concerning how individual cells in the cardiac mesoderm acquire unique fates. We shall use genetics and molecular biology to identify transcriptional regulators of genes with restricted patterns of expression in the dorsal vessel, and to understand how unique cells types arise and differentiate from within the cardiac mesoderm. There is now convincing evidence that the molecular mechanisms of cardiac specification and differentiation are strongly conserved through evolution, and we believe that this will also prove to be the case for the acquisition of unique cell types with the cardiac lineage, as proposed here. Therefore our research will have direct relevance to the understanding of vertebrate heart development including in humans. Furthermore, since a number of congenital heart defects have recently been shown to arise from mutation of cardiac transcription factors, our studies regarding the transcriptional control of heart cell fate are likely to provide critical basic information for understanding the mechanisms of cardiac disease in vertebrates.