The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature
The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature
复制标题
DOI：
10.1242/dev.02141
复制
发表时间：
2005-12-01
期刊：
影响因子：
4.6
通讯作者：
Bader, DM
中科院分区：
文献类型：
--
作者：
Wilm, B;Ipenberg, A;Bader, DM
大多数内脏器官位于体腔内，并被间皮覆盖。在心脏发育过程中，心外膜细胞（间皮细胞）移动到心脏并覆盖心脏，经历上皮-间质转化（EMT），随后分化为内皮细胞和血管平滑肌细胞。这被认为是血管形成的独特过程。尽管如此，心脏和肠道之间的结构和发育相似性使我们测试了一个假设，即一个保守或相关的机制可能会调节肠道的血管发育，肠道与心脏相似，位于体腔中。通过使用分子遗传学，活体染料命运映射，器官培养和免疫组织化学的组合，我们证明，serummesothelium是血管发生细胞在发育中的小鼠肠道的主要来源。我们的研究表明，肠道最初没有间皮细胞，但表达Wilm's肿瘤蛋白（Wt 1）的间皮细胞移动到肠道。随后，这些细胞的一个子集经历EMT并在整个肠道中迁移。使用Wt 1-Cre遗传谱系标记的sereprazole细胞及其后代，我们证明，这些细胞分化为平滑肌的所有主要血管的肠系膜和肠道。我们的数据揭示了一个保守的机制，血管形成体腔器官，并为我们了解脊椎动物器官发生和血管缺陷的肠道有重大影响。
Most internal organs are situated in a coelomic cavity and are covered by a mesothelium. During heart development, epicardial cells (a mesothelium) move to and over the heart, undergo epithelial-mesenchymal transition (EMT), and subsequently differentiate into endothelial and vascular smooth muscle cells. This is thought to be a unique process in blood vessel formation. Still, structural and developmental similarities between the heart and gut led us to test the hypothesis that a conserved or related mechanism may regulate blood vessel development to the gut, which, similar to the heart, is housed in a coelomic cavity. By using a combination of molecular genetics, vital dye fate mapping, organ culture and immunohistochemistry, we demonstrate that the serosal mesothelium is the major source of vasculogenic cells in developing mouse gut. Our studies show that the gut is initially devoid of a mesothelium but that serosal mesothelial cells expressing the Wilm's tumor protein (Wt1) move to and over the gut. Subsequently, a subset of these cells undergoes EMT and migrates throughout the gut. Using Wt1-Cre genetic lineage marking of serosal cells and their progeny, we demonstrate that these cells differentiate to smooth muscle of all major blood vessels in the mesenteries and gut. Our data reveal a conserved mechanism in blood vessel formation to coelomic organs, and have major implications for our understanding of vertebrate organogenesis and vascular deficiencies of the gut.