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The formation of functional blood vessels consists of several steps including the degradation of basement membrane, endothelial cell proliferation, migration and coordination to form 3D lumenized structure.During directional migration toward the gradient of pro-angiogenic factors, the endothelial cells, especially the tip cells need filopodia to sense the environment and exert the pulling force.Filopodia is a well-known structure which is mainly assembled with actin filaments.However, little is known about how the actin filaments were packed into the filopodia.Here, using an inducible endothelial-specific angiomotin (Amot) knockout mouse model, we show that the blood vessel network in the retina could not migrate and expend properly to the edge of the retina at the postnatal stage in the absence of angiomotin.Even the glia and astrocyte pattern are not affected, we do find that there is a dramatically morphology defect of tip cell filopodia.In vitro evidence also showed that Amot bind to actin and cadherin 11 (CDH11), which is crucial for cell migration.Furthermore,the growth of transplanted LLC tumors and tumors of MMTV-PyMT transgenic mice was inhibited when angiomotin was knocked out specifically at vascular endothelial cells.Taken together, these data indicated that angiomotin probably is a novel therapeutic target in the future for inhibiting solid tumor growth.