ZIC3 shapes digit morphogenesis in avian
Bibliographic record
Abstract
Through the evolutionary diversification of birds, a variety of digit morphologies have evolved as adaptations to diverse environments, with the regression of the anterior digits being a remarkable phenomenon. Transcriptomic analysis of chicken limb development has revealed molecular signatures in the anterior digits, among which Zic family member 3 (Zic3) stands out as a unique highly expressed transcription factor. However, the function of Zic3 in digit development in birds remains unclear. In this study, we investigated the expression pattern of Zic3 across five phylogenetically diverse avian species. Our analysis revealed a consistent Zic3 expression pattern in species from Neoaves and Palaeognathae, except for the ostrich. Ostrich hindlimbs exhibited increased Zic3 expression and an extended expression range from the first toe to the second toe. By locally expanding the expression domain of Zic3 in chicken anterior hindlimb buds we obtained a phenotype similar to that of early ostrich feet, characterized by significant shortening of digits I and II. We further performed mRNA Sequencing (mRNA-Seq) of the Zic3-overexpressed autopods and found that Zic3 inhibited skeletal development through multiple pathways, including the Wnt signaling pathway, ECM-receptor interaction and Focal adhesion. Our results reveal a pivotal role for Zic3 in anterior digits and identify its downstream regulatory mediators in birds.
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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) | 0.000 | 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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".