Study of Drosophila Heart Tube Assembly

描述（由申请人提供）：人类的许多心脏异常可归因于早期胚胎发育期间的心脏缺陷。从昆虫到人类，调节心脏发育的遗传途径是保守的。昆虫的心脏是一个线性管，类似于脊椎动物心脏发育早期形成的线性管。昆虫心脏的简单结构以及分子和遗传工具的可用性使得果蝇心脏成为研究脊椎动物心脏发生早期事件的有吸引力的模型系统。定向细胞迁移负责使特定的心脏祖细胞在胚胎中线形成线性心管。细胞表面受体与细胞外基质中的分子的相互作用被认为是有助于血管组织的组装。然而，很少有人知道什么具体的指导线索参与这一过程。Slit是昆虫和人类共同的细胞外基质分子。Slit及其受体蛋白Robo和Robo2在发育中的果蝇心脏中表达。在缺少Slit或Robo蛋白的胚胎中观察到心管组装的严重缺陷，表明这些分子在这一过程中起着重要作用。狭缝影响心管组装的确切机制尚未确定，这是本提案中提出的研究重点。

DESCRIPTION (provided by applicant): Many cardiac abnormalities in humans can be attributed to defects in the heart during early embryogenesis. Genetic pathways that regulate cardiac development are conserved from insects to humans. The insect heart is a linear tube that is analogous to the linear tube that forms during early stages of vertebrate heart development. The simple structure of the insect heart and the availability of molecular and genetic tools make the heart of the fruit fly an attractive model system for the study of the early events of vertebrate cardiogenesis. Directed cell migration is responsible for bringing specified heart progenitor cells to form the linear heart tube at the midline of the embryo. Interactions of cell surface receptors with molecules in the extracellular matrix are considered to be instrumental for assembly of vascular tissues. However, little is known about what specific guidance cues are participating in this process. Slit is an extracellular matrix molecule that is common to both insects and humans. Slit and its receptor proteins Robo and Robo2 are expressed in the developing Drosophila heart. Severe defects in the assembly of the heart tube are observed in embryos missing the Slit or Robo proteins, indicating that these molecules play an important role in this process. The precise mechanism by which Slit affects heart tube assembly has yet to be determined and is the focus of the research presented in this proposal.