4.7 Article

Fgfbp1 promotes blood-brain barrier development by regulating collagen IV deposition and maintaining Wnt/β-catenin signaling

Journal

DEVELOPMENT
Volume 147, Issue 16, Pages -

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.185140

Keywords

Blood-brain barrier; Fgfbp1; Wnt/beta-catenin signaling; Basement membrane; Collagen IV

Funding

  1. Fondation Leducq [15CDV-02]
  2. National Institutes of Health/National Institute of Mental Health [R01 MH112849]
  3. National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01 NS107344]
  4. Vetenskapsradet (Swedish Research Council)
  5. Knut och Alice Wallenbergs Stiftelse
  6. Associazione Italiana per la Ricerca sul Cancro (AIRC) [18683, 21320]
  7. AIRC 5x1000 call 'Metastatic disease: the key unmet need in oncology' of the MYNERVA project [21267]
  8. European Research Council (project EC-ERC-V-EPC) [742922]
  9. Initial Training Networks BtRAIN (H2020 Marie Sklodowska-Curie Actions) [675619]
  10. Fondazione Cariplo [2014-1038, 2016-0461]
  11. Fondazione Telethon [GGP14149]
  12. European Research Council (ERC) [742922] Funding Source: European Research Council (ERC)
  13. Marie Curie Actions (MSCA) [675619] Funding Source: Marie Curie Actions (MSCA)

Ask authors/readers for more resources

Central nervous system (CNS) blood vessels contain a functional blood-brain barrier (BBB) that is necessary for neuronal survival and activity. Although Wnt/beta-catenin signaling is essential for BBB development, its downstream targets within the neurovasculature remain poorly understood. To identify targets of Wnt/beta-catenin signaling underlying BBB maturation, we performed a microarray analysis that identified Fgfbp1 as a novel Wnt/beta-catenin-regulated gene in mouse brain endothelial cells (mBECs). Fgfbp1 is expressed in the CNS endothelium and secreted into the vascular basement membrane during BBB formation. Endothelial genetic ablation of Fgfbp1 results in transient hypervascularization but delays BBB maturation in specific CNSregions, as evidenced by both upregulation of Plvap and increased tracer leakage across the neurovasculature due to reduced Wnt/beta-catenin activity. In addition, collagen IV deposition in the vascular basement membrane is reduced in mutant mice, leading to defective endothelial cell-pericyte interactions. Fgfbp1 is required cell-autonomously in mBECs to concentrate Wnt ligands near cell junctions and promote maturation of their barrier properties in vitro. Thus, Fgfbp1 is a crucial extracellular matrix protein during BBB maturation that regulates cell-cell interactions and Wnt/beta-catenin activity.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available