TY - JOUR
T1 - A transgenic zebrafish model for the in vivo study of the blood and choroid plexus brain barriers using claudin 5
AU - van Leeuwen, Lisanne Martine
AU - Evans, Robert J.
AU - Jim, Kin Ki
AU - Verboom, Theo
AU - Fang, Xiaoming
AU - Bojarczuk, Aleksandra
AU - Malicki, Jarema
AU - Johnston, Simon Andrew
AU - van der Sar, Astrid Marijke
PY - 2018
Y1 - 2018
N2 - 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, probably, choroid plexus (CP) structure and function in vertebrates. 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.
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, probably, choroid plexus (CP) structure and function in vertebrates. 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85042509216&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29437557
U2 - https://doi.org/10.1242/bio.030494
DO - https://doi.org/10.1242/bio.030494
M3 - Article
C2 - 29437557
SN - 2046-6390
VL - 7
JO - Biology open
JF - Biology open
IS - 2
M1 - bio030494
ER -