MYOCYTE PROLIFERATION IN THE EMBRYONIC CHICK HEART

胚胎心肌细胞退出DNA合成，以及 控制这一关键事件的因素在心肌生长和 分化，将在正常和实验改变中进行研究 胚胎雏鸟的心脏。对雏鸡和公鸡的标记研究 已经确定了DNA合成活动的地区差异 胚胎管状心脏，提出了以下假设： 1)对不扩散的承诺是初始阶段的关键一步 心脏偏侧性和环状的测定； 2)静止型心肌细胞沿肌环内曲聚集。 管状心脏和沿最早的脑室小梁延伸 心室传导组织的前体；新静止的细胞 从内部被招募到这个小梁网络的外围 心室游离壁的层层。 具体的实验将解决以下问题： 1)这种静止的肌细胞何时何地首次出现(标记和 测绘实验)？是这样的细胞的时间和分布 反侧(维甲酸)模型中的群体改变 培养雏鸡的梯度或细胞松弛素晶体)？ 2)对不扩散的承诺能否与已知的 传导组织的标志物(相关免疫染色，原位 生长因子、同源异型盒基因7的杂交、EM/放射自显影 &8，心脏连接蛋白)？是否履行了对不扩散的承诺 在小梁网络的边缘或核心，这一承诺是 是突然的还是渐进的？ 3)逆转录病毒感染如何改变心肌细胞的增殖 针对基因的截短或反义序列的表达 与正常的静止状态(同源盒-8或连接蛋白)相关？ 对这些研究的实验答案将检验所述的假设 超越并促进我们描述脊椎动物的长期目标 心脏发育的细节足以理解并最终 预防人类先天性心脏病。

The withdrawal of embryonic cardiac myocytes from DNA-synthesis, and factors controlling this key event in myocardial growth and differentiation, will be studied in normal and experimentally altered hearts of embryonic chicks. Labelling studies in both chicks and rates have defined regional differences in DNA-synthetic activity within the embryonic tubular heart that suggest the following hypotheses: 1) the commitment to non-proliferation is a key step in initial determination of cardiac laterality and looping; 2) quiescent myocytes massed along the inner curvature of the looped tubular heart and extending along the earliest ventricular trabeculae are the precursors of ventricular conducting tissue; newly quiescent cells are recruited to the periphery of this trabecular network from the inner layers of the ventricular free walls. Specific experiments will address the following questions: 1) When and where do such quiescent myocytes first appear (marking and mapping experiments) ? Is the timing and distribution of such cell populations altered in models of reversed laterality (retinoic acid gradients or cytochalasin crystals in cultured chicks)? 2) Can the commitment to non-proliferation be correlated with known markers of conducting tissues (correlative immunostaining, in situ hybridization, EM/autoradiography for growth factors, homeobox genes 7 & 8, cardiac connexins)? Does the commitment to non-proliferation occur at the periphery or core of the trabecular network and is this commitment sudden or gradual? 3) How is myocyte proliferation altered by retroviral infection and expression of truncated or anti-sense sequences for genes specifically correlated with normal quiescence (homeobox-8 or connexins)? Experimental answers to these studies will test the hypotheses stated above and further our long-range objective of describing vertebrate cardiac development in detail sufficient to understand and eventually prevent congenital heart disease in the human.