Myocyte proliferation in the embryonic chick heart

描述（由申请人提供）：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，其长期目标是阐明先天性畸形（如室间隔缺损）的机制。建议的实验和详细的解剖学研究直接建立从我们的映射限制心肌细胞增殖作为一个形态发生的影响，在鸡胚心脏和物理条件作为一个机械的影响，在这个过程中。具体来说，该项目扩展了最近对早期传导组织的关注，作为一种显著的生长缓慢的组织。分化的肌肉的（辛勤工作的）网络，以检查1）在诱导的室间隔缺损（VSD）中传导组织和迁移的神经嵴衍生物之间的明显相互作用，2）肌细胞调节、传导组织的分化和与其他组织的相互作用的物理因素，（3）哺乳动物发育过程的异同。 目的1）鸡心室间隔缺损的发生机制。动力学的关键细胞群体和瓣膜定位在广泛不同的鸡模型诱导室间隔缺损将进行比较的假设下，常见形式的缺陷谱将共享共同的偏差，这些指标。 目的2）对早期发育和分隔的潜在物理影响将在人工心肌管和微型解剖外植体的短期培养物中建模和测试;将在离体灌注心脏和心脏肥大的卵内模型中研究类似的挑战，体外凝胶塌陷研究现已推迟。 目的3）哺乳动物中的相关研究：a）在胚胎和新生大鼠中的选定实验被设计用于检查：i）传导组织分化和成熟到成年的时间过程; ii）在出口分隔的中间阶段的组织运动、细胞分裂和分化的动力学。iii）新生儿主动脉结扎，以监测肥大挑战中传导组织的可塑性。B）在华盛顿和伦敦对大鼠和人类胚胎收集物进行的描述性研究。将比较一系列胚胎的流出结构重建的瓣膜部位的明显旋转和出口肌肉组织通过凋亡或转分化的消失。

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.