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Role of the novel protein family CAMSAP in heart, muscle and tracheal development

新型蛋白质家族 CAMSAP 在心脏、肌肉和气管发育中的作用

基本信息

批准号：
7624648
负责人：
AARON N JOHNSON
金额：
$ 3.35万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-07 至 2009-08-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7624648
关键词：
Address Affect Anterior Area Calculi Calmodulin Cardiac Cardiovascular system Cell Adhesion Cell fusion Collection Computer Systems Development Defect Development Disease Drosophila genus Drosophila melanogaster Embryo Embryonic Development Embryonic Heart Event Excision Fibroblasts Future Genes Genetic Genetic Screening Goals Heart Heart Hypertrophy Human In Situ Hybridization Insecta Mammals Mesoderm Molecular Morphogenesis Morphology Mus Muscle Muscle Development Muscle Fibers Mutation Myoblasts Myocardium Names Organogenesis Pathway interactions Pattern Phenotype Phosphorus Play Protein Family Proteins Respiratory System Role Skeletal Muscle Spectrin Syncope System Tissues Transgenes Tube Vertebrates Yeasts angiogenesis cardiogenesis cell motility congenital heart disorder fly gain of function insight loss of function mutation member mutant novel precursor cell protein expression protein structure function skeletal tool tumor progression

项目摘要

DESCRIPTION (provided by applicant): Identifying the mechanisms that govern heart development is a necessary step to advance our understanding of congenital heart diseases in humans. Since the molecular mechanisms regulating heart development are well conserved between insects and mammals, the powerful genetic tools in Drosophila can be used to identify novel regulators of cardiogenesis. We recently performed a genetic screen for regulators of embryonic heart development in Drosophila and identified over 120 genes whose function is required for proper cardiogenesis. One of these regulators, a novel gene named dCAMSAP, is expressed in discrete domains of the embryonic mesoderm including the heart and muscle precursor cells as well as in the embryonic tracheal system. Embryos bearing a loss-of-function mutation in dCAMSAP do not complete heart closure which causes the heart to tear as the mesoderm extends along the anterior-posterior axis of the embryo. Since the formation of a linear heart tube is a common developmental event in flies and vertebrates, the role of CAMSAP proteins may be highly conserved. In addition to heart closure defects, dCAMSAP mutants show developmental defects in muscles analogous to vertebrate skeletal muscle including both myoblast fusion defects and myotube guidance defects. Finally, the morphology of the insect respiratory system (the tracheal system), whose development is similar to vertebrate angiogenesis, is also affected in dCAMSAP mutant embryos. dCAMSAP is a member of a well conserved yet completely novel protein family with representative members in both humans and mice. The overall goal of this project is to define the molecular mechanisms whereby dCAMSAP regulates heart, skeletal (somatic) muscle, and tracheal system development and to assess the extent to which these mechanisms have been conserved in mammals. These studies will provide fundamental insights into the mechanisms regulating cardiovascular and skeletal muscle development and disease.

描述(由申请人提供)：确定控制心脏发育的机制是促进我们对人类先天性心脏病的理解的必要步骤。由于调控心脏发育的分子机制在昆虫和哺乳动物之间非常保守，果蝇中强大的遗传工具可以用来识别心脏发生的新调节因子。我们最近对果蝇胚胎心脏发育的调节因子进行了遗传筛选，并确定了120多个基因，这些基因的功能是正常心脏发生所必需的。其中一个名为dCAMSAP的新基因在胚胎中胚层的离散结构域中表达，包括心脏和肌肉前体细胞以及胚胎气管系统。携带dCAMSAP功能丧失突变的胚胎不能完全关闭心脏，这会导致心脏撕裂，因为中胚层沿着胚胎的前后轴延伸。由于线形心管的形成是苍蝇和脊椎动物常见的发育事件，因此CAMSAP蛋白的作用可能是高度保守的。除了心脏关闭缺陷外，dCAMSAP突变体还显示出类似于脊椎动物骨骼肌的肌肉发育缺陷，包括成肌细胞融合缺陷和肌管引导缺陷。最后，在dCAMSAP突变胚胎中，昆虫呼吸系统(气管系统)的形态也受到影响，其发育类似于脊椎动物的血管生成。DCAMSAP是一个保守而全新的蛋白质家族的成员，在人类和小鼠中都有代表性的成员。该项目的总体目标是确定dCAMSAP调节心脏、骨骼(躯体)肌和气管系统发育的分子机制，并评估这些机制在哺乳动物中的保守程度。这些研究将为调节心血管和骨骼肌发育和疾病的机制提供基本的见解。