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

Abstract

Recruitment and adhesion of pericytes to endothelial cells represents a critical step in angiogenesis. We previously demonstrated the expression of neural (N)-cadherin at contact zones between pericytes and endothelial cells in embryonic chicken brain. To elucidate N-cadherin function in early angionenesis, we injected functionally blocking antibodies on embryonic days 4 and 5 into the tectal ventricle of chicken embryos. Brains were morphologically and immunocytochemically investigated on embryonic day 6. Blocking N-cadherin function resulted in defective pericyte adhesion, increased pericyte recruitment and disturbed vascular morphogenesis. Increased pericyte recruitment did not involve elevated pericytic proliferation. Concomitant disruption of ependymal adherens junctions and of endothelial-pericytic adhesion resulted in massive hemorrhaging in the basal forebrain, in misdirected endothelial sprouting, and ectopic vascularization. Morphological investigation of control embryos on embryonic days 4 and 5 indicated the initial involvement of pericytes in stabilization of angiogenic capillary sprouts. Together these results suggest that N-cadherin mediates adhesion, recognition, and signaling between pericytes and endothelial cells required for normal vascular morphogenesis.