Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity

Ivan Bassi, Moshe Grunspan, Gideon Hen, Kishore A. Ravichandran, Noga Moshe, Laura Gutierrez-Miranda, Stav R. Safriel, Daria Kostina, Amitay Shen, Carmen Almodovar and Karina Yaniv ()
Additional contact information
Ivan Bassi: Weizmann Institute of Science
Moshe Grunspan: Weizmann Institute of Science
Gideon Hen: Weizmann Institute of Science
Kishore A. Ravichandran: University of Bonn
Noga Moshe: Weizmann Institute of Science
Laura Gutierrez-Miranda: Weizmann Institute of Science
Stav R. Safriel: Weizmann Institute of Science
Daria Kostina: Weizmann Institute of Science
Amitay Shen: Weizmann Institute of Science
Carmen Almodovar: University of Bonn
Karina Yaniv: Weizmann Institute of Science

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract The neurovascular unit (NVU) is a complex multicellular structure that helps maintain cerebral homeostasis and blood-brain barrier (BBB) integrity. While extensive evidence links NVU alterations to cerebrovascular diseases and neurodegeneration, the underlying molecular mechanisms remain unclear. Here, we use zebrafish embryos carrying a mutation in Scavenger Receptor B2, a highly conserved endolysosomal protein expressed predominantly in Radial Glia Cells (RGCs), to investigate the interplay among different NVU components. Through live imaging and genetic manipulations, we demonstrate that compromised acidification of the endolysosomal compartment in mutant RGCs leads to impaired Notch3 signaling, thereby inducing excessive neurogenesis and reduced glial differentiation. We further demonstrate that alterations to the neuron/glia balance result in impaired VEGF and Wnt signaling, leading to severe vascular defects, hemorrhages, and a leaky BBB. Altogether, our findings provide insights into NVU formation and function and offer avenues for investigating diseases involving white matter defects and vascular abnormalities.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52365-8 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:15:y:2024:i:1:d:10.1038_s41467-024-52365-8

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

DOI: 10.1038/s41467-024-52365-8

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 ().