Myocyte proliferation in the embryonic chick heart

描述（由申请人提供）：这个为期五年的项目继续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性畸形（如室间隔缺陷）的机制。我们提出的实验和详细的解剖研究直接建立在我们对鸡胚胎心脏中受限制的肌细胞增殖的形态发生影响和在这一过程中物理条件的机械影响的绘图基础上。具体来说，本项目扩展了最近对早期传导组织的关注，作为一个显著的生长缓慢（艰苦工作）的分化肌肉网络，研究1)传导组织和移入的神经嵴衍生物在诱导室间隔缺损（VSD）中的明显相互作用，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)哺乳动物发育过程中的异同。

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.