N-cadherin mediates pericytic-endothelial interaction during brain angiogenesis in the chicken

Recruitment and adhesion of pericytes to endothelial cells represents a cri tical step in angiogenesis, We previously demonstrated the expression of ne ural (N)-cadherin at contact zones between pericytes and endothelial cells in embryonic chicken brain. To elucidate N-cadherin function in early angio nenesis, we injected functionally blocking antibodies on embryonic days 4 a nd 5 into the tectal ventricle of chicken embryos, Brains were morphologica lly and immunocytochemically investigated on embryonic day 6. Blocking N-ca dherin function resulted in defective pericyte adhesion, increased pericyte recruitment and disturbed vascular morphogenesis. Increased pericyte recru itment did not involve elevated pericytic proliferation, Concomitant disrup tion of ependymal adherens junctions and of endothelial-pericytic adhesion resulted in massive hemorrhaging in the basal forebrain, in misdirected end othelial sprouting, and ectopic vascularization. Morphological investigatio n of control embryos on embryonic days 4 and 5 indicated the initial involv ement of pericytes in stabilization of angiogenic capillary sprouts, Togeth er these results suggest that N-cadherin mediates adhesion, recognition, an d signaling between pericytes and endothelial cells required for normal vas cular morphogenesis. (C) 2000 Wiley-Liss, Inc.