PUBLICATION
Activation of Wnt/β-catenin in neural progenitor cells regulates blood-brain barrier development and promotes neuroinflammation
- Authors
- Sebo, D.J., Ali, I., Fetsko, A.R., Trimbach, A.A., Taylor, M.R.
- ID
- ZDB-PUB-250129-8
- Date
- 2025
- Source
- Scientific Reports 15: 34963496 (Journal)
- Registered Authors
- Taylor, Michael R.
- Keywords
- Blood?Brain barrier (BBB), Endothelial cells (ECs), Neural progenitor cells (NPCs), Neuroinflammation, Wnt/?-catenin, Zebrafish
- MeSH Terms
-
- Neural Stem Cells*/metabolism
- Blood-Brain Barrier*/metabolism
- Microglia/metabolism
- Animals
- Animals, Genetically Modified*
- Neuroinflammatory Diseases*/metabolism
- Neuroinflammatory Diseases*/pathology
- Wnt Signaling Pathway*
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Endothelial Cells/metabolism
- beta Catenin*/metabolism
- PubMed
- 39875426 Full text @ Sci. Rep.
Citation
Sebo, D.J., Ali, I., Fetsko, A.R., Trimbach, A.A., Taylor, M.R. (2025) Activation of Wnt/β-catenin in neural progenitor cells regulates blood-brain barrier development and promotes neuroinflammation. Scientific Reports. 15:34963496.
Abstract
The central nervous system (CNS) requires specialized blood vessels to support neural function within specific microenvironments. During neurovascular development, endothelial Wnt/β-catenin signaling is required for BBB development within the brain parenchyma, whereas fenestrated blood vessels that lack BBB properties do not require Wnt/β-catenin signaling. Here, we used zebrafish to further characterize this phenotypic heterogeneity of the CNS vasculature. Using transgenic reporters of Wnt/β-catenin transcriptional activity, we found an inverse correlation between activated Wnt/β-catenin signaling in endothelial cells (ECs) versus non-ECs within these distinct microenvironments. Our results indicated that the level of Wnt/β-catenin signaling in non-ECs may regulate Wnt/β-catenin activity in adjacent ECs. To further test this concept, we generated a transgenic Tet-On inducible system to drive constitutively active β-catenin expression in neural progenitor cells (NPCs). We found that dose-dependent activation of Wnt/β-catenin in NPCs caused severe deficiency in CNS angiogenesis and BBB development. Additionally, we discovered a significant increase in the proliferation of microglia and infiltration of peripheral neutrophils indicative of a stereotypical neuroinflammatory response. In conclusion, our results demonstrate the importance of proper Wnt/β-catenin signaling within specific CNS microenvironments and highlights the potentially deleterious consequences of aberrant Wnt activation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping