Progressive mural cell deficiencies across the lifespan in a foxf2 model of Cerebral Small Vessel Disease
Bibliographic record
Abstract
Abstract While developmental origins are suspected for many adult diseases, the lifespan effects of developmental perturbations have not been well studied. 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 of small vessels. In humans, reduced FOXF2 is associated with an increased stroke risk and SVD. We use a zebrafish partial foxf2 loss of function to model its effect on small vessel biology through development and aging. In the zebrafish, foxf2 is expressed in brain vascular pericytes and promotes vascular stability. We find that the initial pool of pericytes in developing foxf2a mutants is strongly reduced without affecting the endothelial network. The few brain pericytes present in mutants have strikingly longer processes and enlarged soma. foxf2a mutant pericytes can partially repopulate the brain after genetic ablation suggesting some recovery is possible. Nonetheless, adult foxf2a mutant brains show regional heterogeneity, with areas of normal pericyte coverage of vessels, but others with severe pericyte depletion. Both pericyte and endothelial morphology is strongly affected in adults. Taken together, foxf2a mutants fail to generate a sufficient initial population of pericytes and the few pericytes remaining have abnormal cell morphology. Over the lifespan foxf2a loss leads to severely abnormal cerebrovasculature. Our work opens new understanding of the progression of genetic forms of human Cerebral Small Vessel Disease.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".