Molecular mechanisms of postnatal angiogenesis and neurogenesis

为了鉴定与girdin基因敲除小鼠表型相关的细胞群体，我们将新产生的girdin基因敲除小鼠与nestin启动子驱动的Cre转基因小鼠杂交，以获得girdin基因条件性敲除小鼠。我们的研究结果表明，nestin细胞谱系中的girdin表达与girdin基因敲除小鼠的表型相关。我们使用了病理性眼部新生血管形成的小鼠模型：在S1416 A基因敲入小鼠中病理性新血管形成减少。结果表明，girdin及其磷酸化在新生血管发育和视网膜病理性新生血管形成中起重要作用。我们还发现，girdin的缺失减弱了体外静脉平滑肌细胞的迁移和增殖以及体内静脉移植物中的内膜增生。此外，我们证明了girdin家族蛋白，Dishevelled相关蛋白Daple，控制非经典Wnt/Rac通路和细胞运动

To identify the cellular population responsible for the phenotype of girdin KO mice, newly generated girdin flox mice were crossed with nestin-promoter driven Cre-transgenic mice to obtain girdin conditional knockout mice.Our findings suggested that girdin expression in nestin cell lineage is responsible for the phenotype of girdin KO mice.We used a mouse model of pathological ocular neovascularization: oxygen-induced retinopathy.Pathological neovascularization was decreased in S1416A knockin mice. The results demonstrate that girdin and its phosphorylation play an important role in neonatal vascular development and in pathological neovascularization in the retina.We also found that depletion of girdin attenuated venous smooth muscle cells migration and proliferation in vitro and intimal hyperplasia in vein grafts in vivo.Moreover, we demonstrated that a girdin family protein, Dishevelled-associating protein Daple, controls the non-canonical Wnt/Rac pathway and cell motility