Progressive mural cell deficiencies across the lifespan in a foxf2 model of cerebral small vessel disease
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".