Developmental expression of ZO-1 antigen in the mouse blood-brain barrier

Tight junction biogenesis during blood-brain barrier development (BBB) in m esencephalon microvessels of mouse embryos of day 9, foetuses of day 15 and 19 and new-born (2-day-old) mice was examined by Light and electron micros copy, using monoclonal antibodies recognizing the tight junction peripheral membrane protein ZO-1. A faint spot-like staining began to be recognizable under the light microscope in day 15 vessels in which the endothelial cell s showed isolated fusion points between the external plasmamembrane leaflet s under the electron microscope. A stronger labelling was present in microv essels of day 19 foetuses and new-born animals when the endothelial tight j unction appeared completely differentiated. In the immunogold study, gold p articles were seen scattered throughout the cytoplasm of endothelial cells of day 15 foetuses. In day 19 foetuses and in the new-born mice, gold parti cles were located only at the cytoplasmic surfaces of the tight junctions. The results indicate that the ZO-1 protein is a specific molecular marker i n the developing brain endothelial tight junctions and that its expression takes place parallel to BBB morphofunctional maturation. (C) 1999 Elsevier Science B.V. All rights reserved.