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

Keng Ioi Vong, Tsz Ching Ma, Baiying Li, Thomas Chun Ning Leung, Wenyan Nong, Sai Ming Ngai, Jerome Ho Lam Hui, Liwen Jiang, Kin Ming Kwan*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Article numbere2009568118
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number6
Publication statusPublished - 9 Feb 2021

Scopus Subject Areas

  • General

User-Defined Keywords

  • Blood-cerebrospinal fluid barrier
  • Choroid plexus
  • Epithelial polarity
  • Microtubules
  • Sox9


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