GENETIC DISSECTION OF HEART MORPHOGENESIS IN ZEBRAFISH

斑马鱼心脏形态发生的基因解剖

• 批准号: 6390463
• 负责人: MARK C FISHMAN
• 金额: $ 41.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6390463
• 关键词: atrium; developmental genetics; fluorescent dye /probe; heart; heart ventricle; histogenesis; molecular cloning; mutant; nonmammalian vertebrate embryology; zebrafish

DESCRIPTION (adapted from investigator's abstract): The investigator's hypothesis is that there are separable genetic pathways which configure the ventricle of the early embryonic heart. Their goal is to identify the genes essential to this patterning and to understand their cellular and embryological mechanisms of action. They focus upon four mutations we discovered which perturb formation of the ventricle in embryonic zebrafish: bs2lb, lonely atrium, and Pandora , mutants lack the ventricle, while the atrium is relatively preserved; heart and soul mutant embryos have ventricular tissue contained within the atrium of the early heart tube. In Specific Aim 1, they propose to examine the hypothesis that these mutations perturb preventricular cells in the embryonic heart field, by examination of cell lineage and patterns of expression of myocardial genes in wild-type and mutant fish. In Specific Aim 2, they propose to clone the four mutations by positional strategies. They believe that these genes provide important insights. First; they provide the necessary linchpins to begin molecular dissection of the steps which configure the ventricle. Second, they speak to an evolutionary issue, because the ventricle is a vertebrate-specific addition along the chordate lineage. Third, these genes may have relevance to congenital disorders, such as hypoplastic heart syndromes, and to potential therapeutic replenishment of contractile myocardium of the failing heart.

描述(改编自调查员摘要)：调查员的 假设存在可分离的遗传途径，它们配置了 早期胚胎心脏的脑室。他们的目标是识别基因 对这种模式至关重要，并了解它们的细胞和胚胎学 行动机制。他们专注于我们发现的四种突变 斑马鱼胚胎脑室的扰动形成：bs2磅，孤独 心房和潘多拉，变种人没有脑室，而心房是 相对保存；心脏和灵魂突变胚胎有心室组织 包含在早期心管的中庭内。在具体目标1中，他们 建议检验这样一种假设，即这些突变干扰了预防 胚胎心野中的细胞，通过细胞谱系和模式的检查 野生型和突变型FISH中心肌基因表达的研究。以特定的目标 2，他们提出通过定位策略克隆这四个突变。他们 相信这些基因提供了重要的见解。首先，它们提供了 必要的关键环节开始分子解剖的步骤，配置 脑室。其次，它们涉及到一个进化问题，因为 脑室是脊椎动物特有的沿着脊索血统的附加物。第三, 这些基因可能与先天性疾病有关，如发育不良。 心脏综合征，以及潜在的治疗补充收缩 衰竭心脏的心肌。