GENETIC DISSECTION OF HEART MORPHOGENESIS IN ZEBRAFISH

斑马鱼心脏形态发生的基因解剖

• 批准号: 2892892
• 负责人: MARK C FISHMAN
• 金额: $ 41.32万
• 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 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2892892
• 关键词: GENETIC; DISSECTION; HEART; MORPHOGENESIS; 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（改编自研究者摘要）：研究者的 假设是有可分离的遗传途径， 早期胚胎心室。他们的目标是找出 对这种模式化和理解它们的细胞和胚胎学至关重要 作用机制。他们专注于我们发现的四种突变， 胚胎斑马鱼心室的扰动形成：bs 2lb，孤独 心房和潘多拉，突变体没有心室，而心房是 相对保存;心脏和灵魂突变胚胎有心室组织 包含在早期心管的心房内。具体目标1， 我建议检查这些突变干扰预防性的假设， 胚胎心脏领域的细胞，通过检查细胞谱系和模式 心肌基因在野生型和突变型鱼中的表达。具体目标 2、他们提出了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，他们提供 必要的关键，开始分子解剖的步骤， 心室第二，他们谈到了一个进化的问题，因为 心室是脊椎动物特有的附加物，沿着脊索动物谱系。第三、 这些基因可能与先天性疾病有关， 心脏综合征，并涉及潜在的治疗性补充收缩 衰竭心脏的心肌