REGULATION OF CARDIAC MYOGENESIS

心肌是最早出现的分化组织之一 胚胎发育，因为正常运作的心脏对胚胎至关重要 发展和生存能力。然而，令人惊讶的是，我们对此知之甚少 心脏的形成，或者说关于调节离散步骤的机制 心肌细胞特化、增殖和转归途径 差异化。在很大程度上，我们缺乏知识可以追溯到 缺乏能够重建心脏关键部位的体外细胞模型 肌肉细胞发育。 我们最近开发了两种体外培养试验，这将使我们能够 以解决有关心脏早期发育的重要问题。 因此，本提案中的研究将使用这些分析来 研究细胞相互作用和生长因子信号分子如何 调控禽类心肌前体细胞的出现 胚胎。一种方法是利用后缘区上胚外植体 和来自前原肠胚的低母细胞，第二种使用离散的区域和 原始条纹内的细胞层和早期的亨森结节 原肠线虫。基于初步研究，我们提出了这颗心脏 肌肉前体细胞因生长因子而变得特异 来自周围细胞层和组织的信号，包括次母细胞， Hensen‘s结节和出现的内胚层。实验将验证这一点 命题通过考察回答与回答之间的归纳相互作用 以及诱导细胞层，从而导致指定的 前心肌细胞，并通过寻找可以诱导 反应细胞层中的心肌。实验还将调查 新形成的内胚层在调节血管内皮细胞发育中的作用 心肌前体细胞，并将研究Tinman(Nkx-2，5)和 MEF2基因表达在心前节律过程中的调节 中胚层。这些研究的结果将增加我们对两者的理解 心脏发育正常和异常，并可能提出改变心脏的方法 心肌细胞的发育或复制。

Heart muscle is among the earliest differentiated tissues to appear in the developing embryo because a functioning heart is crucial to embryonic development and viability. We know surprisingly little, however, about how the heart forms, or about the mechanisms that regulate discrete steps along the pathway of heart muscle cell specification, proliferation and differentiation. In large part, our lack of knowledge can be traced to the absence of in vitro cell models that can recreate key aspects of heart muscle cell development. We have recently developed two in vitro culture assays that will enable us to address important questions concerning early heart development. Accordingly, the research in this proposal will use these assays to investigate how cellular interactions and growth factor signaling molecules regulate the appearance of heart muscle precursor cells in the avian embryo. One assay utilizes explants of posterior marginal zone epiblast and hypoblast from pregastrula embryos, the second uses discrete areas and cell layers within the primitive streak and Hensen's node of early gastrulae. Based upon preliminary studies, we have proposed that heart muscle precursor cells become specified in response to growth factor signals from surrounding cell layers and tissues, including the hypoblast, Hensen's node and emerging endoderm. Experiments will test this proposition by investigating the inductive interactions between responding and inducing cell layers that lead to the appearance of specified premyocardial cells, and by searching for growth factors that can induce heart muscle in responsive cell layers. Experiments will also investigate the potential role of newly formed endoderm in regulating development of heart muscle precursor cells, and will investigate how Tinman (Nkx-2,5) and MEF2 gene expression is regulated during specification of precardiac mesoderm. Results of these studies will increase our understanding of both normal and abnormal heart development and may suggest ways to alter heart development or the replication of cardiac myocytes.