THE RELATIONSHIP BETWEEN FOREGUT AND CARDIAC MORPHOGENESIS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 这项工作的总体目标是确定前肠形态发生在伴随的 心脏形态发生，在发育阶段，当这两个管状器官形成时， 胚胎中线具体来说，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，形成管状心脏，由外部心肌组成， 细胞外基质（ECM）层将细胞膜分为细胞外基质层和内内皮层。随心管 在融合过程中，心管保持短暂的开放并与腹侧前肠接触。 我们已经表明，管状心脏的组成部分（心肌细胞，内皮细胞，ECM （三）被纳入中央。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， 细胞心肌细胞自主运动，并观察所得的前肠和心脏表型， 延时录像随后的计算分析将使我们能够量化细胞自主运动， in vivo体内，under下experimentally实验disturbed干扰conditions条件.拟议的目标如下： 目的1：破坏前肠门/AIP的消退（从而使前肠延长），并监测 心管融合期间对心脏形态发生的动态（3D+时间=4D）影响（HH 9 -10）。 目的2：确定在心前中胚层和/或相邻内胚层中表达的FGF是否具有作用， 对心前细胞中线迁移和/或心管融合期间的细胞运动性的影响。 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分开， 并确定前肠形成在管状心脏形成中的作用。在哪个单元格上获得的数据 群体表现出活跃的细胞运动性，组织水平的位移将在未来发挥什么作用 努力模拟鸟类心脏管的形成。

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.