Cardiomyocyte Proliferation and Ventricular Morphogenesis

心肌细胞增殖和心室形态发生

• 批准号: 9927738
• 负责人: Henry M Sucov
• 金额: $ 38.89万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-09 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927738
• 关键词: Address; Adult; Arteries; Automobile Driving; Biochemical; Birth; Blood Vessels; CXCL12 gene; Cardiac Myocytes; Cells; Child; Congenital Heart Defects; Coronary; Coronary Circulation; Coronary Vessels; Coronary artery; Development; Developmental Process; Embryo; Embryonic Development; Embryonic Heart; Endocardium; Endothelium; Epicardium; Erythropoietin; Fetal Liver; Funding; Gene Expression; Goals; Growth; Heart; In Vitro; Individual; Injury; Insulin-Like Growth Factor II; Liver; Logic; Metabolic; Mitogens; Modeling; Morphogenesis; Mus; Mutant Strains Mice; Myocardium; Natural regeneration; Nature; Neonatal; Organ; Process; Proteins; Regulation; Respiratory Diaphragm; Role; Signal Transduction; Source; Surface; Testing; Thick; Time; Tissues; Veins; Venous; Ventricular; Work; base; cardiac regeneration; cardiogenesis; coronary perfusion; coronary vasculature; in vivo; insight; mouse development; novel strategies; paracrine; postnatal; programs; vasculogenesis

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.

项目摘要 心外膜在妊娠中期小鼠心脏发育过程中具有几个关键功能。 本项目的持续重点是单独理解这些过程， 将它们的发育和调节逻辑与心脏的其他方面相互整合 发育，以及整个胚胎发育的更大背景 在目的1中，我们考虑心外膜有丝分裂信号诱导心肌细胞的功能， 增殖，特别是解决的性质，调节有丝分裂原表达的前， 和妊娠中期发育的胎盘后时期。主要目标是确认 心室腔生长与胎盘功能协调。 我们最近的工作确定了CXCL12是冠状动脉血管生成所必需的。以 CXCL12作为器官特异性、动脉特异性和免疫调节剂的独特特征的优势。 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 更好地定义冠状神经丛成熟过程的策略， 基于CXCL12信号传导的需要，并开发一种 一种新的策略来可视化静脉到动脉的重编程过程。 尽管心肌细胞增殖和冠状动脉血管发生在出生时就已完成，但两者都 在新生小鼠心脏损伤后被重新激活。在目标3中，我们研究了同样的 在妊娠中期心脏形态发生中支持这些过程的信号被重新利用， 新生儿心脏的再生。

项目成果

Igf Signaling is Required for Cardiomyocyte Proliferation during Zebrafish Heart Development and Regeneration.

• DOI: 10.1371/journal.pone.0067266
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Huang Y;Harrison MR;Osorio A;Kim J;Baugh A;Duan C;Sucov HM;Lien CL
• 通讯作者: Lien CL

CXCL12 Signaling Is Essential for Maturation of the Ventricular Coronary Endothelial Plexus and Establishment of Functional Coronary Circulation.

• DOI: 10.1016/j.devcel.2015.03.018
• 发表时间: 2015-05-26
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Cavallero, Susana;Shen, Hua;Yi, Christopher;Lien, Ching-Ling;Kumar, S. Ram;Sucov, Henry M.
• 通讯作者: Sucov, Henry M.