Function of Dell in Embryonic Development

戴尔在胚胎发育中的作用

基本信息

批准号：
13670027
负责人：
HIDAI Chiaki
金额：
$ 1.98万
依托单位：
Nihon University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670027/
关键词：
Endothelia cell Development Angiogenesis 形態形成心筋肥大

项目摘要

Vascular remodeling is an essential process that allows the primary vascular plexus to develop into matured vasculature during embryonic development. Gene-targeting experiments have revealed that such remodeling is regulated by the products of several different genes. These include secreted molecules, receptor tyrosine kinases, and transcription factors. In mutant mice lacking these molecules, the primary vascular plexus fails to assemble into large vessels during development. Unfortunately, these 'loss of function' experiments do not advance our understanding of how vascular remodeling controls branching morphogenesis during development. Dell is an extracellular matrix protein that is exclusively expressed in embryonic endothelial cells. To investigate Dell function in developing embryos, we used a cytomegalovirus enhancer seguence to generate Dell overexpression mice, using. In transgenic mice, the total vascular bed was decreased in the alimentary tracts because of accelerated vascular remodeling at mid stage gestation. In addition to the quantitative change, overexpression of Dell reorganized vascular branching patterns, resulting in dendritic vessels. The present study indicates that Dell overexpression accelerates vascular remodeling and causes changes in branching morphogenesis during embryonic development

血管重塑是胚胎发育过程中初级血管丛发育成成熟脉管系统的重要过程。基因靶向实验表明，这种重塑是由几种不同基因的产物调节的。这些包括分泌分子、受体酪氨酸激酶和转录因子。在缺乏这些分子的突变小鼠中，初级血管丛在发育过程中无法组装成大血管。不幸的是，这些“功能丧失”实验并没有增进我们对血管重塑如何控制发育过程中分支形态发生的理解。 Dell 是一种细胞外基质蛋白，仅在胚胎内皮细胞中表达。为了研究 Dell 在发育胚胎中的功能，我们使用巨细胞病毒增强子序列来生成 Dell 过度表达小鼠。在转基因小鼠中，由于妊娠中期血管重塑加速，消化道中的总血管床减少。除了数量上的变化外，Dell 的过度表达还重组了血管分支模式，产生了树突状血管。本研究表明 Dell 过度表达加速血管重塑并导致胚胎发育过程中分支形态发生的变化