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Formation and function of the meningeal arachnoid barrier around the developing mouse brain
Developmental Cell ( IF 10.7 ) Pub Date : 2023-03-29 , DOI: 10.1016/j.devcel.2023.03.005
Julia Derk 1 , Christina N Como 2 , Hannah E Jones 3 , Luke R Joyce 4 , Sol Kim 3 , Brady L Spencer 4 , Stephanie Bonney 1 , Rebecca O'Rourke 1 , Brad Pawlikowski 1 , Kelly S Doran 4 , Julie A Siegenthaler 5
Affiliation  

The arachnoid barrier, a component of the blood-cerebrospinal fluid barrier (B-CSFB) in the meninges, is composed of epithelial-like, tight-junction-expressing cells. Unlike other central nervous system (CNS) barriers, its' developmental mechanisms and timing are largely unknown.

Here, we show that mouse arachnoid barrier cell specification requires the repression of Wnt-β-catenin signaling and that constitutively active β-catenin can prevent its formation. We also show that the arachnoid barrier is functional prenatally and, in its absence, a small molecular weight tracer and the bacterium group B Streptococcus can cross into the CNS following peripheral injection. Acquisition of barrier properties prenatally coincides with the junctional localization of Claudin 11, and increased E-cadherin and maturation continues after birth, where postnatal expansion is marked by proliferation and re-organization of junctional domains. This work identifies fundamental mechanisms that drive arachnoid barrier formation, highlights arachnoid barrier fetal functions, and provides novel tools for future studies on CNS barrier development.



中文翻译:


发育中小鼠大脑周围脑膜蛛网膜屏障的形成和功能



蛛网膜屏障是脑膜中血脑脊液屏障 (B-CSFB) 的组成部分,由上皮样紧密连接表达细胞组成。与其他中枢神经系统(CNS)障碍不同,其发育机制和时间在很大程度上是未知的。


在这里,我们表明,小鼠蛛网膜屏障细胞规范需要抑制 Wnt-β-连环蛋白信号传导,并且组成型活性 β-连环蛋白可以阻止其形成。我们还表明,蛛网膜屏障在产前是有功能的,如果没有蛛网膜屏障,小分子量示踪剂和 B 族链球菌细菌可以在外周注射后进入中枢神经系统。产前屏障特性的获得与 Claudin 11 的连接定位相一致,并且 E-钙粘蛋白的增加和成熟在出生后继续,其中出生后扩展的标志是连接域的增殖和重组。这项工作确定了驱动蛛网膜屏障形成的基本机制,突出了蛛网膜屏障的胎儿功能,并为未来研究中枢神经系统屏障发育提供了新的工具。

更新日期:2023-03-29
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