Transcription Factors Pax6 and AP-2α Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase B
Bibliographic record
Abstract
Pax6 is a paired box containing transcription factor that resides at the top of a genetic hierarchy controlling eye development. It continues to be expressed in tissues of the adult eye, but its role in this capacity is unclear. Pax6 is present in the adult corneal epithelium, and we showed that the amount of Pax6 is increased at the migrating front as the epithelium resurfaces the cornea after injury. We also showed that Pax6 controls activity of the transcriptional promoter for the matrix metalloproteinase, gelatinase B (gelB; MMP-9) in cell culture transfection studies. gelB expression is turned on at the migrating epithelial front in the cornea, and it coordinates and effects aspects of epithelial regeneration. We define here two positively acting Pax6 response elements in the gelB promoter. Pax6 binds directly to one of these sites through the paired DNA-binding domain. It binds the second site indirectly by interaction with AP-2alpha, a transcription factor that also exerts control over eye development. Pax6 control of gelB expression was examined in vivo by using a corneal reepithelialization model in mice heterozygous for a Pax6 paired-domain mutation (Sey(+/-)). A reduced Pax6 dosage in these mice resulted in a loss of gelB expression at the migrating epithelial front. This effect was correlated with an increase in inflammation and the rate of reepithelialization, a finding consistent with the phenotype of gelB knockout mice. Together, these data indicate that Pax6 controls activity of the gelB promoter through cooperative interactions with AP-2alpha and support an active role for Pax6 in maintenance and repair of the adult corneal epithelium.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.002 | 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".