PUBLICATION
Glial betaPix is essential for blood vessel development in the zebrafish brain
- Authors
- Chiu, S., Zhou, Q., Xiao, C., Bai, L., Zhu, X., Ding, W., Xiong, J.W.
- ID
- ZDB-PUB-260117-14
- Date
- 2026
- Source
- eLIFE 14: (Journal)
- Registered Authors
- Xiong, Jing-Wei
- Keywords
- betaPix, brain blood vessel, brain hemorrhage, conditional knockout, developmental biology, zebrafish
- MeSH Terms
-
- Animals
- Blood Vessels*/embryology
- Blood Vessels*/growth & development
- Blood-Brain Barrier
- Brain*/blood supply
- Brain*/embryology
- Guanine Nucleotide Exchange Factors*/genetics
- Guanine Nucleotide Exchange Factors*/metabolism
- Neovascularization, Physiologic*
- Neuroglia*/metabolism
- Neuroglia*/physiology
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41543887 Full text @ Elife
Citation
Chiu, S., Zhou, Q., Xiao, C., Bai, L., Zhu, X., Ding, W., Xiong, J.W. (2026) Glial betaPix is essential for blood vessel development in the zebrafish brain. eLIFE. 14:.
Abstract
The formation of blood-brain barrier and vascular integrity depends on the coordinated development of different cell types in the brain. Previous studies have shown that zebrafish bubblehead (bbh) mutant, which has mutation in the betaPix locus, develops spontaneous intracerebral hemorrhage during early development. However, it remains unclear in which brain cells betaPix may function. Here, we established a highly efficient conditional knockout method in zebrafish by using homology-directed repair-mediated knockin and knockout technology and generated betaPix conditional trap (betaPixct) allele in zebrafish. We found that betaPix in glia, but neither neurons, endothelial cells, nor pericytes was critical for glial and vascular development and integrity, thus contributing to the formation of blood-brain barrier. Single-cell transcriptome profiling revealed that microtubule aggregation signaling stathmins and pro-angiogenic transcription factors Zfhx3/4 were downregulated in glial and neuronal progenitors, and further genetic analysis suggested that betaPix may act upstream on the PAK1-Stathmin and Zfhx3/4-Vegfaa signaling to regulate glia migration and angiogenesis. Therefore, this work reveals that glial betaPix plays an important role in brain vascular development in zebrafish embryos and possibly human cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping