THE RELATIONSHIP BETWEEN FOREGUT AND CARDIAC MORPHOGENESIS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项拟议工作的总体目标是确定前肠形态发生在伴随中的作用 心脏形态发生，在发育阶段，当这两个管状器官在 胚胎中线。具体地说，我们试图确定内胚层折叠在运动中的作用 将双侧心脏前体带到中线，形成由外心肌组成的管状心脏 由一层细胞外基质(ECM)隔开的心内膜层。跟随心导管 融合时，心导管暂时开放并与腹侧前肠接触。 我们已经证明，管状心脏的组成部分(心肌细胞、心内膜细胞、细胞外基质 选民)被带到中线。在发育中的胚胎中，细胞运动可以是 被视为以下因素的净结果：1)定向的细胞自主运动(相对于细胞环境的迁移) 以及2)组织的大规模位移/变形。我们试图扰乱组织运动和 细胞心肌细胞自主运动，并观察由此产生的前庭和心脏表型 延时录音。随后的计算分析将使我们能够量化细胞的自主运动性， 在体内，在实验扰动的条件下。建议的目标如下： 目的1：阻断前肠门/AIP(从而前肠延长)的消退，并监测 动态(3D+时间=4D)对心管融合过程中心脏形态发生的影响(HH9-10)。 目的2：确定在心脏前中胚层和/或邻近内胚层表达的成纤维细胞生长因子是否有作用。 在心脏前细胞中线迁移和/或心管融合过程中对细胞运动的影响。 这项工作的长期目标是确定前肠和心脏形态发生是否可以解偶联， 并确定前肠形成在管状心脏形成中所起的作用。从哪个单元格获取的数据 群体表现出活跃的细胞运动，以及组织水平的位移在未来将发挥什么作用 对鸟类心管形成进行模拟的努力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall objective of the proposed work is to define the role of foregut morphogenesis in concomitant cardiac morphogenesis, at developmental stages when these two tubular organs are forming at the embryonic midline. Specifically, we seek to determine the role of endodermal folding in the movements that bring the bilateral cardiac precursors to the midline to form a tubular heart, comprised of an outer myocardial layer and an inner endocardial layer separated by a layer of extracellular matrix (ECM). Following heart tube fusion, the cardiac tube remains transiently open to and in contact with the ventral foregut. We have shown that components of the tubular heart (myocadial cells, endocardial cells, ECM constituents) are brought to the midline. In the context of the developing embryo, cellular movement can be seen as a net result of: 1) directed cell autonomous motility (migration relative to the cellular environment) and 2) large-scale displacements/deformations of the tissue. We seek to perturb both tissue movements and cell myocardial cell autonomous motility and to observe the resulting foregut and cardiac phenotypes using time-lapse recordings. Subsequent computational analyses will allow us to quantify cell autonomous motility, in vivo, under experimentally perturbed conditions. Proposed aims are as follows: Aim 1: To disrupt regression of the anterior intestinal portal/AIP (and thus foregut elongation) and to monitor dynamically (3D+time=4D) effects on heart morphogenesis during heart tube fusion (HH9-10). Aim 2: To determine if FGF, expressed in the precardiac mesoderm and/or adjacent endoderm, has an effect on cell motility during precardiac cell midline-migration and/or heart tube fusion. The long-term goal of this work is to determine if foregut and cardiac morphogenesis can be uncoupled, and to define what role foregut formation plays in formation of a tubular heart. Data obtained on which cell populations exhibit active cell motility and what role tissue-level displacements play will be used in future efforts to model avian heart tube formation.