• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Mechanisms of cardiovascular development.
【24h】

Mechanisms of cardiovascular development.

机译：心血管发育的机制。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Epithelial to mesenchymal transition (EMT) is an essential process during embryogenesis for the development of organ systems, including the heart and its vasculature. The development of both coronary vessels and heart valves depends on EMT. In this dissertation, we first present data demonstrating that increased oligosaccharide hyaluronan (o-HA) levels after EMT induction within atrioventricular (AV) valves leads to a decrease in EMT due to the induction of VEGF expression. Regulated EMT inhibition prevents the formation of hyperplastic valves. Next, we show that the proepicardium, which provides the precursor cells required for epicardial and coronary vessel development, migrates to the developing heart via direct contact of multicellular proepicardial villi to the developing myocardium. This shifts the paradigm from a migration consisting of floating cysts to one of direct contact and differential adhesion forces to form the initial epicardium. A subset of epicardial cells undergoes EMT, migrates into the developing heart, and differentiates into cardiac fibroblast, vascular endothelial, and smooth muscle cells. In order to more effectively study epicardial EMT in vitro, we developed several new methods for the in vitro study of coronary vessel development. We developed an improved protocol for isolating embryonic myocyte cells, for use in co-cultures with epicardial cells. This co-culture system allows investigation into the effects of myocyte derived soluble factors upon epicardial EMT and mesenchymal cell differentiation. We also present a protocol for isolating epicardial clonal colonies from an epicardial cell line derived from the ImmortoMouse. These clones provided direct evidence that the epicardium is a heterogeneous population of cells. These unique clones allow for to study into specific epicardial cell lineages and phenotypes. Finally, we provide data defining the expression of Wnts within the developing heart and the role may play during epicardial EMT. We conclude that canonical Wnts are both necessary and sufficient to inhibit epicardial EMT. These results provide the first direct evidence for a role of Wnt proteins during coronary vessel development. Collectively our results provide significant advancements in our understanding of EMT regulation during cardiac development.
机译：上皮到间质转化（EMT）是胚胎发生过程中器官系统（包括心脏及其脉管系统）发育的重要过程。冠状血管和心脏瓣膜的发展都取决于EMT。在本文中，我们首先提出数据，证明房室（AV）瓣膜内EMT诱导后寡糖透明质酸（o-HA）水平升高导致EMT降低，这归因于VEGF表达的诱导。调节的EMT抑制可防止增生性瓣膜的形成。接下来，我们显示前庭，它提供了心外膜和冠状动脉发育所需的前体细胞，通过多细胞前庭绒毛直接与发育中的心肌接触而迁移到发育中的心脏。这将范式从由漂浮的囊肿组成的迁移转移到直接接触力和差分粘附力之一，从而形成初始心外膜。心外膜细胞的一部分经历EMT，迁移到发育中的心脏，并分化为心脏成纤维细胞，血管内皮细胞和平滑肌细胞。为了更有效地体外研究心外膜EMT，我们开发了几种体外研究冠状动脉发育的新方法。我们开发了一种改进的协议，用于分离胚性心肌细胞，用于与心外膜细胞共培养。该共培养系统允许研究心肌细胞衍生的可溶性因子对心外膜EMT和间充质细胞分化的影响。我们还提出了一个协议，用于从源自ImmortoMouse的心外膜细胞系中分离心外膜克隆菌落。这些克隆提供了直接证据，表明心外膜是细胞的异质群体。这些独特的克隆可用于研究特定的心外膜细胞谱系和表型。最后，我们提供了定义Wnts在发育中心脏内的表达及其在心外膜EMT期间可能发挥作用的数据。我们得出结论，规范性Wnts既是必要的也是足以抑制心外膜EMT的。这些结果为Wnt蛋白在冠状动脉发育过程中的作用提供了第一个直接证据。总体而言，我们的结果为我们在心脏发育过程中对EMT调节的理解提供了重大进展。

著录项

  • 作者

    Rodgers, Laurel Speilman.;

  • 作者单位

    The University of Arizona.;

  • 授予单位 The University of Arizona.;
  • 学科 Biology Molecular.;Biology Cell.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 187 p.
  • 总页数 187
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;细胞生物学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号