N-cadherin expression in endothelial cells during early angiogenesis in the eye and brain of the chicken: relation to blood-retina and blood-brain barrier development

The factors responsible for the induction and maintenance of blood-brain ba rrier properties are still undefined. The process of blood-brain barrier fo rmation is thought to take place in a two-stage manner: the initial commitm ent of vascular sprouts by neuroectodermal cells may be followed by the sta bilization of barrier properties. In the present study, we investigated the expression pattern of neural (N)-cadherin during early angiogenesis in the brain and the pecten oculi of the chicken. The pecten has been introduced previously as a model for the investigation of the formation and maturation of barrier properties in the central nervous system. Whereas perineural an d choroid vessels remained immunonegative for N-cadherin, vascular sprouts invading both the brain and the pecten primordium acquired anti-N-cadherin immunoreactivity, Confocal laser scanning and immunoelectron microscopy ind icated that the antigen was located at the ablumenal endothelial membrane i n contact with subendothelial cells. With the onset of barrier differentiat ion as determined by junctional restriction of the tight junction protein o ccludin, N-cadherin labelling rapidly decreased. Specific intraneuroectoder mal upregulation and decline of endothelial N-cadherin was confirmed by in situ hybridization and suggests that N-cadherin expression by cerebral and pecteneal endothelial cells represents an initial and transient signal whic h may be involved in the commitment of early blood vessels to express blood -brain and blood-retina barrier properties.