RT Journal Article SR Electronic T1 A transgenic zebrafish model for the in vivo study of the blood and choroid plexus brain barriers using claudin 5 JF bioRxiv FD Cold Spring Harbor Laboratory SP 180653 DO 10.1101/180653 A1 Lisanne Martine van Leeuwen A1 Robert J. Evans A1 Kin Ki Jim A1 Theo Verboom A1 Xiaoming Fang A1 Aleksandra Bojarczuk A1 Jarema Malicki A1 Simon Andrew Johnston A1 Astrid Marijke van der Sar YR 2017 UL http://biorxiv.org/content/early/2017/08/25/180653.abstract AB The central nervous system (CNS) has specific barriers that protect the brain from potential threats and tightly regulate molecular transport. Despite the critical functions of the CNS barriers, the mechanisms underlying their development and function are not well understood, and there are very limited experimental models for their study. Claudin 5 is a tight junction protein required for blood brain barrier (BBB) and choroid plexus (CP) barrier structure and function in humans. Here, we show that the gene claudin 5a is the zebrafish orthologue with high fidelity expression, in the BBB and CP barriers, that demonstrates the conservation of the BBB and CP between humans and zebrafish. Expression of claudin 5a correlates with developmental tightening of the BBB and is restricted to a subset of the brain vasculature clearly delineating the BBB. We show that claudin 5a expressing cells of the CP are ciliated ependymal cells that drive fluid flow in the brain ventricles. Finally, we find that CP development precedes BBB development and that claudin 5a expression occurs simultaneously with angiogenesis. Thus, our novel transgenic zebrafish represents an ideal model to study CNS barrier development and function, critical in understanding the mechanisms underlying CNS barrier function in health and disease.