Regulation of cardiac chamber morphogenesis in zebrafish

斑马鱼心室形态发生的调节

• 批准号: 6970395
• 负责人: DEBORAH YELON
• 金额: $ 38.03万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6970395
• 关键词: alternatives to animals in research; cardiac myocytes; cardiogenesis; cell biology; cell cell interaction; cell growth regulation; cell migration; cell morphology; endocardium; genetic mapping; heart ventricle; hemodynamics; histogenesis; in situ hybridization; molecular biology; molecular cloning; transmission electron microscopy; zebrafish

DESCRIPTION (provided by applicant): The embryonic vertebrate heart is composed of 2 major chambers, a ventricle and an atrium, each with a characteristic morphology that defines its functional capacity. Congenital heart defects are often associated with dysmorphic cardiac chambers, but the regulation of cardiac chamber morphogenesis is not well understood. Cardiac chamber morphogenesis can be divided into 2 major phases: heart tube assembly, in which bilateral precursor populations unite to form a tube, and chamber emergence, in which this simple cylinder transforms into a series of morphologically discrete chambers. The long-term goal of our research is to identify the cellular and molecular mechanisms that regulate these 2 phases of chamber morphogenesis. Using the zebrafish as a model organism, we can combine embryologic and genetic approaches, using high-resolution live imaging to determine how key genes influence cardiomyocyte behavior. Our preliminary time-lapse analyses of heart tube assembly suggest that this process is driven by multiple genes that collaborate to regulate regional differences in directed cardiomyocyte movements. Additionally, our initial morphometric analyses of chamber emergence suggest that this process is governed. by both intrinsic and extrinsic factors that control regional changes in cardiomyocyte morphology. Finally, our recent studies of novel mutations suggest that the slow fuse and change of heart genes are critical regulators of heart tube assembly and chamber emergence, respectively. Building on this foundation, we propose to test (1) how cardiomyocyte movements are regulated by a critical mass of cells, formation of polarized epithelia, interactions with endoderm and endocardium, and slow fuse function, and (2) how cardiomyocyte morphology is regulated by hemodynamics, sarcomere integrity, interactions with the endocardium, and change of heart function. Together, these studies will reveal essential regulatory mechanisms of cardiogenesis and also enrich our understanding of general paradigms for organ formation.

描述（由申请人提供）：胚胎脊椎动物心脏由2个主要腔室组成，一个心室和一个中庭，每个脊椎动物都具有定义其功能能力的特征形态。先天性心脏缺陷通常与畸形心脏腔有关，但心脏腔形态发生的调节尚不清楚。心脏室形态发生可以分为两个主要阶段：心管组件，其中双侧前体种群团结起来形成管子，并出现腔室，其中这个简单的圆柱体转化为一系列形态上离散的室。我们研究的长期目标是确定调节室形态发生这两个阶段的细胞和分子机制。使用斑马鱼作为模型生物，我们可以使用高分辨率实时成像来结合胚胎学和遗传方法，以确定关键基因如何影响心肌细胞行为。我们对心脏管组件的初步延时分析表明，该过程是由多个基因驱动的，这些基因协作以调节定向心肌细胞运动的区域差异。此外，我们对腔室出现的最初形态计量学分析表明，该过程受到控制。通过控制心肌细胞形态的区域变化的内在和外在因素。最后，我们最近对新型突变的研究表明，心脏基因的缓慢融合和变化分别是心管组装和腔室出现的关键调节因子。在基础的基础上，我们建议测试（1）如何通过临界细胞，极化上皮的形成，与内胚层和心内心脏的相互作用以及融合速度的功能来调节心肌细胞运动，以及（2）心肌细胞形态如何受到心态，肌动力学，肌动力学，肌动力学，肌瘤，与内骨的相互作用和内核功能。总之，这些研究将揭示心脏发生的基本调节机制，并丰富我们对器官形成的一般范式的理解。