MYOCYTE PROLIFERATION IN THE EMBRYONIC CHICK HEART

描述（改编自申请人的摘要）：增殖， 终末分化和特定群体的最终命运 心肌细胞将在1）正常的传导系统中进行研究 发育中的鸡心脏，2）在体外肌管制备中，和3） 鸡胚诱发特定的心脏畸形。 最近的研究 已经确定了鸡心脏最早的终末分化， 最初的循环和跟踪的贡献，这种早期的小梁和 内壁肌细胞进入永久性中枢传导系统， 完全成形的心脏 在孵育第2-3天标记的一些细胞仍然存在 标记至少100天后孵化;一些分支的 胚胎传导系统通过凋亡性细胞死亡而消失， 分隔期。 这些研究是中央的基础。 这一建议假设，早期终末分化的具体 在成环和分隔过程中，心肌细胞的数量至关重要 心脏传导组织的出现和正常形成， 到最终的四腔心脏的正常形态发生。 的 首席研究员现在提出了一个为期五年的实验计划，以： 目的1）在空间方面映射心脏传导组织的出现 和终端分化的时间模式和持久性 内壁肌细胞的特化祖细胞群。 目标2）探索 改变几何形状和物理负荷条件对心肌细胞的影响 人工心肌管的增殖和终末分化 和体外培养的预成环心脏。 3）广泛比较三个 室间隔缺损的不同鸡模型，以测试常见的 传导组织配置的正常模式的变化， 在上面建立的终端差异。 这些实验是为了 为了测试关于1）潜在的物理因素的特定假设， 传导系统的形成和成熟，2） 胚胎心肌细胞增殖、终末分化或死亡; 和3）在广泛不同的情况下，这种模式中的潜在共同变化 心脏畸形的模型。

DESCRIPTION (adapted from the applicant's abstract): Proliferation, terminal differentiation and eventual fate of specific populations of cardiac myocytes will be studied in 1) the conduction system of the normally developing chick heart, 2) in an in vitro muscular tube preparation, and 3) in chick embryos provoked to specific cardiac malformations. Recent studies have identified earliest terminal differentiation in chick heart during initial looping and traced the contribution of such early trabecular and inner wall myocytes into the definitive central conduction system of the fully-formed heart. Some cells labeled on days 2-3 of incubation remain labeled at least 100 days post hatching; some of the branches of the embryonic conduction system disappear through apoptotic cell death during the septation period. These studies are the basis for the central hypothesis of this proposal, that early terminal differentiation of specific populations of cardiac myocytes during looping and septation is critical both to the emergence and proper formation of cardiac conduction tissue and to normal morphogenesis of the definitive four-chambered heart. The principal investigator now proposes a five-year program of experiments to: Aim 1) Map the emergence of cardiac conduction tissue in terms of spatial and temporal patterns of terminal differentiation and persistence of specialized progenitor populations of inner wall myocytes. Aim 2) Explore effects of altered geometry and physical load conditioning upon myocyte proliferation and terminal differentiation in artificial myocardial tubes and prelooping hearts cultured in vitro. Aim 3) Compare three widely divergent chick models of ventricular septal defect to test for common variation in the normal patterns of conduction tissue disposition and terminal differentiation established above. These experiments are designed to test specific hypotheses concerning 1) the physical factors underlying the formation and maturation of the conduction system, 2) the decision of embryonic cardiac myocytes to proliferate, terminally differentiate, or die; and 3) potentially common variations in such patterns in widely differing models of cardiac malformation.