MYOCYTE PROLIFERATION IN THE EMBRYONIC CHICK HEART

描述(改编自申请人的摘要)：扩散， 黄曲霉特定种群的末端分化和最终命运 心肌细胞将在1)正常心脏传导系统中进行研究。 雏鸡心脏发育，2)体外肌管制剂，3) 在小鸡胚胎中引发特定的心脏畸形。最新研究 已发现雏鸡心脏最早的终末分化 并追踪这种早期的骨小梁和 内壁肌细胞进入终末中枢传导系统 完全成形的心。一些在孵育2-3天标记的细胞仍然存在 在孵化后至少100天贴上标签；一些树枝 胚胎传导系统因细胞凋亡而消失 分隔期。这些研究是中央 这一提议的假说是，特异体的早期末端分化 循环和间隔期间心肌细胞的数量是至关重要的 对于心脏传导组织的出现和正常形成以及 最终的四心室心脏的正常形态发生。这个 首席研究员现在提出了一项为期五年的实验计划，以： 目的1)绘制心脏传导组织在空间上的出现图 和终末分化和持续的时间模式 内壁心肌细胞的特化祖细胞群体。目标2)探索 改变几何构型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 和体外培养的前循环心脏。目标3)广泛比较三个 发散型雏鸡室间隔缺损模型的建立 传导组织处置的正常模式的变异和 顶端分化建立在上面。这些实验是经过精心设计的 测试关于1)潜在物理因素的特定假设 传导系统的形成和成熟，2)决策 胚胎心肌细胞增殖、终末分化或死亡； 以及3)这些模式中潜在的共同变异 心脏畸形模型。

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.