气候变化领域集成服务门户(CCPortal): SOX9-COL9A3-dependent regulation of choroid plexus epithelial polarity governs blood-cerebrospinal fluid barrier integrity

CCPortal

DOI	10.1073/pnas.2009568118
	SOX9-COL9A3-dependent regulation of choroid plexus epithelial polarity governs blood-cerebrospinal fluid barrier integrity
	Vong K.I.; Ma T.C.; Li B.; Leung T.C.N.; Nong W.; Ngai S.M.; Hui J.H.L.; Jiang L.; Kwan K.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	The choroid plexus (CP) is an extensively vascularized neuroepithelial tissue that projects into the brain ventricles. The restriction of transepithelial transport across the CP establishes the blood-cerebrospinal fluid (CSF) barrier that is fundamental to the homeostatic regulation of the central nervous system microenvironment. However, the molecular mechanisms that control this process remain elusive. Here we show that the genetic ablation of Sox9 in the hindbrain CP results in a hyperpermeable blood-CSF barrier that ultimately upsets the CSF electrolyte balance and alters CSF protein composition. Mechanistically, SOX9 is required for the transcriptional up-regulation of Col9a3 in the CP epithelium. The reduction of Col9a3 expression dramatically recapitulates the blood-CSF barrier defects of Sox9 mutants. Loss of collagen IX severely disrupts the structural integrity of the epithelial basement membrane in the CP, leading to progressive loss of extracellular matrix components. Consequently, this perturbs the polarized microtubule dynamics required for correct orientation of apicobasal polarity and thereby impedes tight junction assembly in the CP epithelium. Our findings reveal a pivotal cascade of SOX9-dependent molecular events that is critical for construction of the blood-CSF barrier. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Blood-cerebrospinal fluid barrier; Choroid plexus; Epithelial polarity; Microtubules; Sox9
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180751
作者单位	School of Life Sciences, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong; AoE Centre for Genomic Studies on Plant-Environment Interaction for Sustainable Agriculture and Food Security, The Chinese University of Hong Kong, Hong Kong; Centre for Cell and Developmental Biology, The Chinese University of Hong Kong, Hong Kong
推荐引用方式 GB/T 7714	Vong K.I.,Ma T.C.,Li B.,et al. SOX9-COL9A3-dependent regulation of choroid plexus epithelial polarity governs blood-cerebrospinal fluid barrier integrity[J],2021,118(6).
APA	Vong K.I..,Ma T.C..,Li B..,Leung T.C.N..,Nong W..,...&Kwan K.M..(2021).SOX9-COL9A3-dependent regulation of choroid plexus epithelial polarity governs blood-cerebrospinal fluid barrier integrity.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Vong K.I.,et al."SOX9-COL9A3-dependent regulation of choroid plexus epithelial polarity governs blood-cerebrospinal fluid barrier integrity".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).