Endothelial Unc5B controls blood-brain barrier integrity

Kevin Boyé, Luiz Henrique Geraldo, Jessica Furtado, Laurence Pibouin-Fragner, Mathilde Poulet, Doyeun Kim, Bryce Nelson, Yunling Xu, Laurent Jacob, Nawal Maissa, Dritan Agalliu, Lena Claesson-Welsh, Susan L. Ackerman and Anne Eichmann ()
Additional contact information
Kevin Boyé: Yale University School of Medicine
Luiz Henrique Geraldo: Yale University School of Medicine
Jessica Furtado: Yale University School of Medicine
Laurence Pibouin-Fragner: Université de Paris, INSERM, PARCC
Mathilde Poulet: Yale University School of Medicine
Doyeun Kim: OliX pharmaceuticals
Bryce Nelson: Yale University School of Medicine
Yunling Xu: Université de Paris, INSERM, PARCC
Laurent Jacob: Université de Paris, INSERM, PARCC
Nawal Maissa: Université de Paris, INSERM, PARCC
Dritan Agalliu: Columbia University Irving Medical Center
Lena Claesson-Welsh: Uppsala University
Susan L. Ackerman: University of California San Diego and Howard Hughes Medical Institute
Anne Eichmann: Yale University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Blood-brain barrier (BBB) integrity is critical for proper function of the central nervous system (CNS). Here, we show that the endothelial Unc5B receptor controls BBB integrity by maintaining Wnt/β-catenin signaling. Inducible endothelial-specific deletion of Unc5B in adult mice leads to BBB leak from brain capillaries that convert to a barrier-incompetent state with reduced Claudin-5 and increased PLVAP expression. Loss of Unc5B decreases BBB Wnt/β-catenin signaling, and β-catenin overexpression rescues Unc5B mutant BBB defects. Mechanistically, the Unc5B ligand Netrin-1 enhances Unc5B interaction with the Wnt co-receptor LRP6, induces its phosphorylation and activates Wnt/β-catenin downstream signaling. Intravenous delivery of antibodies blocking Netrin-1 binding to Unc5B causes a transient BBB breakdown and disruption of Wnt signaling, followed by neurovascular barrier resealing. These data identify Netrin-1-Unc5B signaling as a ligand-receptor pathway that regulates BBB integrity, with implications for CNS diseases.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28785-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28785-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28785-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().