Function of Dell in Embryonic Development

血管重塑是胚胎发育过程中使初级血管丛发育成成熟血管的重要过程。基因打靶实验表明，这种重塑受几个不同基因的产物调控。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”的实验并没有促进我们对血管重塑如何在发育过程中控制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在胚胎发育中的作用，我们使用巨细胞病毒增强子序列来产生DELL过表达的小鼠。在转基因小鼠中，由于妊娠中期血管重塑加速，消化道总血管床减少。除了数量上的变化，戴尔的过度表达重组了血管分支模式，导致树枝状血管。目前的研究表明，在胚胎发育过程中，戴尔的过度表达会加速血管重塑，并导致分支形态发生的变化

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