Cardiomyocyte Proliferation and Ventricular Morphogenesis

项目摘要 心外膜在妊娠中期小鼠心脏发育过程中有几个重要的功能。 本项目的持续重点是逐一了解这些过程，并 将他们的发展和调控逻辑与心脏的其他方面相互结合 发育，以及整个胚胎发育的更大背景下 在目标1中，我们考虑了心外膜有丝分裂信号诱导心肌细胞的功能。 增殖，并特别涉及在前有丝分裂原表达的调节性质。 胎盘后中期发育。主要目标是确认如何 脑室发育与胎盘功能相协调。 我们最近的工作证实，CXCL12是冠状动脉血管生成所必需的。拿走 利用CXCL12作为器官特定、动脉特定和 旁分泌作用的血管成熟因子，在目标2中，我们提出了几个实验 更好地确定冠状神经丛成熟过程的策略，解决 冠状动脉内皮细胞对CXCL12信号的需求，并开发一种 可视化静脉到动脉重编程过程的新策略。 虽然心肌细胞增殖和冠状动脉血管生成是通过出生完成的，但两者 在损伤后的新生小鼠心脏中重新激活。在目标3中，我们研究了相同的 在妊娠中期心脏形态发生过程中支持这些过程的信号在 用于再生的新生儿心脏。

Project Summary The epicardium has several critical functions during midgestation mouse heart development. The continuing focus of this project is to understand these processes individually and to integrate their developmental and regulatory logic with each other, with other aspects of heart development, and with the larger context of overall embryo development In Aim 1, we consider the function of epicardial mitogenic signaling that induces cardiomyocyte proliferation, and in particular address the nature of regulation of mitogen expression in the pre- and post-placental period of midgestation development. A primary goal is to confirm how ventricular chamber growth is coordinated with placental function. Our recent work established that CXCL12 is required for coronary vasculogenesis. Taking advantage of the unique features of CXCL12 as an organ-specific, arterial-specific, and paracrine-acting vascular maturation factor, in Aim 2 we propose several experimental strategies to better define the process of coronary plexus maturation, to resolve the source of coronary arterial endothelium based on requirement for CXCL12 signaling, and to develop a novel strategy to visualize the process of venous to arterial reprogramming. Although cardiomyocyte proliferation and coronary vasculogenesis are completed by birth, both are reactivated in the neonatal mouse heart after injury. In Aim 3, we examine how the same signals that support these processes in midgestation heart morphogenesis are reutilized in the neonatal heart for regeneration.