van Leeuwen Lisanne Martine, Evans Robert J, Jim Kin Ki, Verboom Theo, Fang Xiaoming, Bojarczuk Aleksandra, Malicki Jarema, Johnston Simon Andrew, van der Sar Astrid Marijke
Department of Medical Microbiology & Infection control, VU Medical Center, Amsterdam 1081HV, The Netherlands.
Department of Pediatric Infectious Diseases & Immunology, VU Medical Center, Amsterdam 1007MB, The Netherlands.
Biol Open. 2018 Feb 2;7(2):bio030494. doi: 10.1242/bio.030494.
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 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 correlates with developmental tightening of the BBB and is restricted to a subset of the brain vasculature clearly delineating the BBB. We show that -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 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.
中枢神经系统（CNS）具有特定的屏障，可保护大脑免受潜在威胁并严格调节分子运输。尽管中枢神经系统屏障具有关键功能，但其发育和功能的潜在机制尚未得到充分了解，并且用于研究它们的实验模型非常有限。Claudin 5是一种紧密连接蛋白，对脊椎动物的血脑屏障（BBB）以及可能的脉络丛（CP）结构和功能是必需的。在这里，我们表明该基因是斑马鱼的直系同源基因，在血脑屏障和脉络丛屏障中具有高保真表达，这证明了人类和斑马鱼之间血脑屏障和脉络丛的保守性。Claudin 5的表达与血脑屏障的发育紧密相关，并仅限于清晰描绘血脑屏障的一部分脑血管系统。我们表明，脉络丛中表达Claudin 5的细胞是纤毛室管膜细胞，可驱动脑室中的液体流动。最后，我们发现脉络丛的发育先于血脑屏障的发育，并且Claudin 5的表达与血管生成同时发生。因此，我们的新型转基因斑马鱼是研究中枢神经系统屏障发育和功能的理想模型，这对于理解中枢神经系统屏障在健康和疾病中的功能机制至关重要。
