دورية أكاديمية
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SOX9-COL9A3-dependent regulation of choroid plexus epithelial polarity governs blood-cerebrospinal fluid barrier integrity.

التفاصيل البيبلوغرافية
العنوان: SOX9-COL9A3-dependent regulation of choroid plexus epithelial polarity governs blood-cerebrospinal fluid barrier integrity.
المؤلفون: Vong KI; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Ma TC; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Li B; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Leung TCN; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Nong W; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Ngai SM; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.; AoE Centre for Genomic Studies on Plant-Environment Interaction for Sustainable Agriculture and Food Security, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Hui JHL; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Jiang L; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.; Centre for Cell and Developmental Biology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Kwan KM; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; kmkwan@cuhk.edu.hk.; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.; Centre for Cell and Developmental Biology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Feb 09; Vol. 118 (6).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Cell Polarity*, Blood/*metabolism , Cerebrospinal Fluid/*metabolism , Choroid Plexus/*metabolism , Collagen Type IX/*metabolism , Epithelial Cells/*cytology , SOX9 Transcription Factor/*metabolism, Animals ; Basement Membrane/metabolism ; Collagen Type IX/genetics ; Electrolytes/cerebrospinal fluid ; Epithelial Cells/metabolism ; Epithelium/metabolism ; Extracellular Matrix/metabolism ; Gene Deletion ; Gene Knockdown Techniques ; Mice, Knockout ; Microtubules/metabolism ; Tight Junctions/metabolism ; Transcription, Genetic ; Mice
مستخلص: 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.
Competing Interests: The authors declare no competing interest.
(Copyright © 2021 the Author(s). Published by PNAS.)
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فهرسة مساهمة: Keywords: Sox9; blood–cerebrospinal fluid barrier; choroid plexus; epithelial polarity; microtubules
المشرفين على المادة: 0 (Collagen Type IX)
0 (Electrolytes)
0 (SOX9 Transcription Factor)
تواريخ الأحداث: Date Created: 20210202 Date Completed: 20210621 Latest Revision: 20240226
رمز التحديث: 20240226
مُعرف محوري في PubMed: PMC8017668
DOI: 10.1073/pnas.2009568118
PMID: 33526661
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.2009568118