Genetic analysis indicates that transcription factors AP-2alpha and Pax6 cooperate in the normal patterning and morphogenesis of the lens.
Bibliographic record
Abstract
PURPOSE: The similar lens phenotypes observed in mice with mutations in the genes encoding either Pax6 or AP-2alpha suggested that these transcription factors work together to regulate specific signaling cascades during lens development. In this study we examined the overlapping expression patterns of Pax6 and AP-2alpha in the developing mouse lens and further investigated their potential cooperative roles through the creation of double heterozygote mice. METHODS: Colocalization of Pax6 and AP-2alpha expression patterns were performed on sections of mouse embryos at embryonic days 9.5, 10.5, 13.5, and 16 as well as on adult sections using immunofluorescence. To test the potential cooperation between these two transcription factors, two mouse strains heterozygous for the genes encoding either Pax6 or AP-2alpha were bred together to produce double heterozygous Pax6(+/lacZ)/AP-2alpha(+/-) mice. Histological examination was then performed on both embryonic and post-natal sections in order to compare double heterozygous Pax6(+/lacZ)/AP-2alpha(+/-) eyes to single heterozygote and wildtype eyes. RESULTS: Examination of the developmental stages showed distinct colocalization of Pax6 and AP-2alpha protein in the anterior lens epithelium. However, Pax6 expression continued further into the transitional zone of the lens whereas AP-2alpha expression ceased just prior to the region where epithelial cells differentiate into fiber cells. Histological investigation of embryonic and post-natal mutant mouse eyes showed that while single Pax6 heterozygote mice exhibited remnants of a corneal-lenticular adhesion, the lens and cornea were physically separated. In contrast, the Pax6(+/lacZ)/AP-2alpha(+/-) double heterozygotes displayed a distinct lens stalk, which protruded towards the surface of the cornea, creating a direct corneal-lenticular attachment. CONCLUSIONS: Colocalization of Pax6 and AP-2alpha was mainly observed in the proliferating central lens epithelium, the same region in which the lens stalk phenotype was observed in the double heterozygous Pax6(+/lacZ)/AP-2alpha(+/-) eyes. The more severe phenotype observed in these double heterozygous mice, as compared to the single heterozygotes, suggests that Pax6 and AP-2alpha may work synergistically to control lens development.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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".