Serosal Mesothelium and Vascularization of the Gut

描述(申请人提供)：我们的数据显示，来自浆膜间皮(SM；肠内相当于心前膜(PE)/心外膜)的一部分细胞经历了上皮/间充质转化(EMT)。这些细胞自由迁移到消化道的所有器官中，并分化为一组不同的细胞，包括肠道的壁状血管生成细胞。因此，SM差异反映了体育发展的特定方面，但它们的发展概况也存在显著差异。虽然SM在发育中具有广泛的作用，但它在血管形成和器官发生中的潜在作用和调节却完全未知。此外，我们还确定了分离的成年SM可以被诱导分化为平滑肌。这表明成年SM具有血管生成潜能，提示SM可能是一种自然产生的用于修复的祖细胞来源。我们的目标将考察三个独立但互动的概念，这些概念与SM在开发和修复方面的潜力有关。目标1将使用异位嫁接来确定SM和PE是否具有互换或内在可变的潜力。目标2将使用谱系和消融模型来确定SM如何调节肠道中的血管形态发生。AIM 3将使用基因标记的SM移植来确定其在调节损伤后血管修复中的作用。综上所述，这些研究将确定SM广泛但仍然鲜为人知的潜力如何调节血管的发育和修复。与公共卫生相关：肠道主要血管的发育尚不清楚。我们的研究将确定胚胎肠道中血管的来源以及形成模式是如何调节的。这些研究将为未来对发育和疾病中异常血管形成的分析奠定基础。

DESCRIPTION (provided by applicant): Our data show that a subset of cells from the serosal mesothelium (SM; the gut equivalent of the proepicardium (PE)/epicardium) undergoes an epithelial/mesenchymal transition (EMT). These cells freely migrate to populate all organs of the alimentary canal and differentiate into a diverse set of cells including mural vasculogenic cells of the gut. Thus, SM differentiation mirrors specific aspects of PE development but significant differences in their developmental profiles also exist. While it is clear that SM has broad roles in development, its potential in and regulation of blood vessel formation and organogenesis is completely unknown. Additionally, we determined that isolated adult SM can be induced to differentiate into smooth muscle. This demonstrates that adult SM retains vasculogenic potential and suggests that the SM may serve as a naturally occurring source of progenitor cells for repair. Our aims will examine three independent yet interactive concepts related to the potential of SM in development and repair. Aim 1 will use heterotopic grafting to determine if SM and PE have interchangeable or inherently variable potential. Aim 2 will use lineage and ablation models to determine how SM regulates blood vessel morphogenesis in the gut. Aim 3 will use genetically-tagged SM transplants to determine its role in regulation of blood vessel repair after injury. Taken together these studies will determine how the broad yet still poorly understood potential of SM regulates vessel development and repair. PUBLIC HEALTH RELEVANCE: Development of the major blood vessels of the gut is not understood. Our studies will determine the source of blood vessels in the embryonic gut and how the pattern of formation is regulated. These studies will form the background for future analysis of abnormal blood vessel formation in development and disease.