Molecular mechanisms of postnatal angiogenesis and neurogenesis

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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