Developmental changes in tight junction protein organization. Immunostaining of occludin and claudin-5 shows endothelial cytoplasmic staining with some linear cell membrane assembly of occludin present at 12 weeks PMA in human fetal telencephalon (A, B). By 14 weeks, linear beaded staining of occludin and claudin-5 becomes evident in the cell membrane (C, D). At 18 weeks, a more mature appearance of nearly linear immunostaining of occludin and claudin-5 occurs. Source: Adapted, with permission, from Virgintino et al. (434).