PUBLICATION
Progressive mural cell deficiencies across the lifespan in a foxf2 model of cerebral small vessel disease
- Authors
- Graff, M.F.E., Heeg, E.E.M., Elliott, D.A., Childs, S.J.
- ID
- ZDB-PUB-260307-13
- Date
- 2026
- Source
- eLIFE 14: (Journal)
- Registered Authors
- Childs, Sarah J.
- Keywords
- blood vessel, developmental biology, mural cells, pericytes, small vessel disease, zebrafish
- MeSH Terms
-
- Animals
- Brain/pathology
- Cerebral Small Vessel Diseases*/genetics
- Cerebral Small Vessel Diseases*/pathology
- Cerebral Small Vessel Diseases*/physiopathology
- Disease Models, Animal
- Forkhead Transcription Factors*/deficiency
- Forkhead Transcription Factors*/genetics
- Forkhead Transcription Factors*/metabolism
- Humans
- Pericytes*/metabolism
- Pericytes*/pathology
- Zebrafish
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41789880 Full text @ Elife
Citation
Graff, M.F.E., Heeg, E.E.M., Elliott, D.A., Childs, S.J. (2026) Progressive mural cell deficiencies across the lifespan in a foxf2 model of cerebral small vessel disease. eLIFE. 14:.
Abstract
Cerebral small vessel disease (SVD) is a leading cause of stroke and dementia and yet is often an incidental finding in aged patients due to the inaccessibility of brain vasculature to imaging. Animal models are important for modelling the development and progression of SVD across the lifespan. In humans, reduced FOXF2 is associated with an increased stroke risk and SVD prevalence in humans. In the zebrafish, foxf2 is expressed in pericytes and vascular smooth muscle cells and is involved in vascular stability. We use partial foxf2 loss of function (foxf2a-/-) to model the lifespan effect of reduced Foxf2 on small vessel biology. We find that the initial pool of pericytes in developing foxf2a mutants is strongly reduced. The few brain pericytes present in mutants have strikingly longer processes and enlarged soma. foxf2a mutant pericytes can partially repopulate the brain after ablation, suggesting some recovery is possible. Despite this capacity, adult foxf2a mutant brains show regional heterogeneity, with some areas of normality and others with severe pericyte depletion. Taken together, foxf2a mutants fail to generate a sufficient initial population of pericytes. The pericytes that remain have abnormal cell morphology. Over the lifespan, initial pericyte deficits are not repaired and lead to severely abnormal cerebrovasculature in adults. This work opens new avenues for modeling progressive genetic forms of human cerebral small vessel disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping