<i>Zic3</i> represses anterior digit development in tetrapods
Bibliographic record
Abstract
Pentadactyl limbs represent a conserved morphological feature among tetrapods, with anterior digits considered more important than posterior digits for refined movement. While posterior digit formation is governed by graded expression of the <italic>Shh</italic> and 5’<italic>Hox</italic> genes, the regulatory mechanisms underlying anterior digit development, especially digit I (DI), remain poorly defined. This study identified an anterior expression pattern of <italic>Zic3</italic> in the limb buds of representative tetrapods, including humans, which exerted an inhibitory effect on skeletal development. <italic>Zic3</italic> was highly expressed in the anterior region of limb buds at early developmental stages, with species-specific divergence emerging during later development. Overexpression of <italic>Zic3</italic> significantly delayed chondrogenesis and ossification, leading to bone shortening but not loss. Furthermore, RNA sequencing demonstrated that <italic>Zic3</italic> down-regulated key genes associated with skeletal development, including <italic>Cytl1</italic>, <italic>Sox9, Ihh</italic>, <italic>Ptch1</italic>, <italic>Runx2</italic>, and <italic>Wnt16</italic>. These findings demonstrate that <italic>Zic3</italic> acts as a conserved inhibitor of anterior skeletal maturation and contributes to the molecular asymmetry of tetrapod limb development.
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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) | 0.001 | 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 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".