COMPUTATIONAL IMAGING OF AVIAN HEART MORPHOGENESIS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在鸟类胚胎中，两侧心脏原基在中线融合形成一个管状结构。随后，该管经历屈曲和旋转的过程;导致环状心脏。我们的长期目标是确定多种遗传和信号缺陷是否汇聚在一个共同的机械联系上，以防止心脏融合-导致贲门裂。已知局部细胞-细胞外基质（ECM）相互作用对于早期心脏发育至关重要。此外，我们提出，全球组织变形直接影响细胞运动和正在进行的重组所需的适当的心管融合的ECM。因此，将测试以下假设：第一，心脏形态发生所需的细胞和ECM组分是从远处募集的;第二，这些“原材料”被不依赖于自主细胞运动的物理组织水平事件置换;第三，适当的心脏形态发生需要细胞集合体和“募集的”ECM原纤维的持续组织水平重组;第四，对机械微环境的扰动，如局部张力场或细胞-ECM相互作用的破坏，将导致可再现的心脏畸形。因此，我们将：1）确定正常和实验扰动胚胎中鸟类双侧心管融合期间中胚层细胞和ECM原纤维位置-命运图; 2）计算可归因于自主运动与组织对流的总细胞位移的分量; 3）计算正常和实验扰动胚胎的心脏形成区域中的应变;以及4）构建包含管状心脏形态发生的预测有限元模型。这些目标将使用DIC和落射荧光时间推移显微镜和随后的计算分析所产生的图像帧来实现。相关性：计算成像数据将表明心脏形态发生过程中机械模式的重要性。预测计算机模型将表征心脏畸形的生物力学，并可能提供信息，以帮助预防相关的心脏缺陷。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the avian embryo, bilateral heart primordia fuse to form a tube at the midline. Subsequently, this tube undergoes a process of flexion and rotation; resulting in a looped heart. Our long-term goal is to determine if multiple genetic and signaling defects converge at a common mechanical nexus to prevent heart fusion - resulting in cardia bifida. It is known that local cell-extracellular matrix (ECM) interactions are critical for early heart development. In addition, we propose that global tissue deformations directly influence cell motion and the ongoing reorganization of the ECM necessary for proper heart tube fusion. Accordingly, the following hypotheses will be tested: First, that cells and ECM components required for heart morphogenesis are recruited from distant sites; Second, that these "raw materials" are displaced by physical tissue-level events that are not dependent on autonomous cell motion; Third, that proper heart morphogenesis requires ongoing tissue-level reorganization of cell collectives and the "recruited" ECM fibrils; and Fourth, that perturbations to the mechanical micro-environment, such as disruption of local tension fields or cell-ECM interactions, will cause reproducible heart malformations. Accordingly, we will: 1) Determine mesodermal cell and ECM fibril position-fate maps during avian bilateral heart tube fusion in normal and experimentally perturbed embryos; 2) Compute the component of total cell displacements attributable to autonomous motion versus tissue convection; 3) Compute strain in the heart-forming regions of normal and experimentally perturbed embryos; and 4) Construct a predictive finite element model encompassing tubular heart morphogenesis. These aims will be accomplished using DIC and epifluorescence time lapse microscopy and subsequent computational analyses of the resulting image frames. RELEVANCE: Computational imaging data will indicate the importance of mechanical patterning during heart morphogenesis. Predictive computer models will characterize the bio-mechanics of heart malformations and may provide information to help prevent related heart defects.