Myocyte proliferation in the embryonic chick heart

描述(申请人提供)：这个为期五年的项目延续了我们对早期心脏形态和功能的发育解剖学和生物物理学的长期兴趣，长期目标是阐明先天畸形的机制，如室间隔缺陷。拟议的实验和详细的解剖学研究直接建立在我们的图谱基础上，即限制的心肌细胞增殖是鸡胚胎心脏的形态发生影响，而物理条件作用是这一过程中的机械影响。具体地说，该项目扩展了最近对早期传导组织的关注，将其作为一个显著缓慢增长(努力工作)的分化肌肉网络，以检查1)在诱导室间隔缺陷(VSD)中传导组织和迁移性神经峰衍生物之间的明显相互作用，2)潜在的肌细胞调节、传导组织的分化和与其他组织相互作用的物理因素，以及3)这些过程在发育哺乳动物中的相似和不同。 目的1)鸡室间隔缺损的发病机制。在假设常见形式的缺陷谱将在这些指标中共享共同偏差的假设下，将比较差异很大的诱导性室间隔缺损鸡模型中关键细胞群体和瓣膜位置的动力学。 目的2)对早期发育和间隔的潜在物理影响将在人工心脏肌管和显微解剖的短期培养中模拟和测试；类似的挑战将在分离的灌流心脏和在体心肌肥大模型中进行研究，体外凝胶崩解研究现已被推迟。 目的3)哺乳动物的相关研究：a)选择胚胎和新生大鼠作为实验对象，研究：(1)输卵管出口间隔中期的组织运动、细胞分裂和分化的动力学过程。3)新生主动脉环扎术，用于监测肥厚刺激时传导组织的可塑性。B)在华盛顿和伦敦对老鼠和人类胚胎收集进行描述性研究。对一系列胚胎的流出结构的重建将比较瓣膜位置的明显旋转和通过细胞凋亡或转分化而消失的流出肌肉系统。

DESCRIPTION (provided by applicant): This five-year project continues our long interest in the developmental anatomy and biophysics of early heart form and function, with the long-range goal of elucidating mechanisms of congenital malformations such as ventricular septal defects. The proposed experiments and detailed anatomical studies build directly from our mapping of restricted myocyte proliferation as a morphogenetic influence in the embryonic chick heart and in physical conditioning as a mechanical influence in this process. Specifically, this project extends recent focus upon early conduction tissue, as a prominently slow-growing (hard working) network of differentiated muscle, to examine 1) apparent interplay between conduction tissues and immigrating neural crest derivatives in induced ventricular septal defects (VSD), 2) physical factors underlying myocyte conditioning, differentiation of conduction tissue and interactions with other tissues, and 3) similarities and differences in these processes in developing mammals. Aim 1) Mechanisms of ventricular septal defect in chick. Kinetics of key cell populations and valve positioning in widely divergent chick models of induced VSD will be compared under the hypothesis that common forms of that defect spectrum will share common deviations in those indices. Aim 2) Potential physical influences on early development and septation will be modeled and tested in artificial cardiac myotubes and short-term cultures of micro,dissected explants; Similar challenges will be studied in isolated perfused hearts and in an in ovo model of cardiac hypertrophy, In vitro gel collapse studies have now been deferred. Aim 3) Correlative studies in mammals: a) Selected experiments in embryonic and neonatal rats are designed to examine: i) The time course of conduction tissue differentiation and maturation into adult it) Kinetics of tissue movements, cell division and differentiation at intermediate stages of outlet septation. iii) Neonatal aortic banding, to monitor plasticity of conduction tissues in hypertrophic challenge. b) Descriptive studies in rats and in human embryo collections at Washington and London. Reconstructions of outflow structures from series of embryos will be compared for apparent rotation of valves sites and disappearance, through apoptosis or transdifferentiation, of outlet musculature.