The relationship between variable SHH signaling and the severity of structural defects in the face and brain
Bibliographic record
Abstract
Embryonic shape plays an important role in the etiology of craniofacial birth defects, yet how morphological variation is generated early in development and contributes to disease incidence is poorly understood. Here we propose a model in which there is a predictable relationship between variation in Shh signaling, the underlying cellular and molecular processes that control growth, embryonic craniofacial shape, and the severity of facial defects. To test these predictions, we induced variation in Shh signaling in chick embryos using a neutralizing antibody (5E1), imaged embryos with µCT, and calculated the relationship of craniofacial shape to dosage. Our preliminary results demonstrate a continuous range of phenotypes, with a fully penetrant phenotype at the highest dose of cells and progressively more variable and less severe phenotypes at lower doses. These results confirm that the Shh pathway acts in a predictable manner on the incidence and severity of craniofacial dysmorphology, particularly in the brain and face. Ongoing analyses are focused on linking these results explicitly to variation in gene expression and cell proliferation. Ultimately, understanding how genetic and developmental mechanisms interact to generate phenotypic variation, from healthy to diseased, will enable both the prediction of facial malformations in utero and corrective genetic therapies in human embryos.
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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 | 0.001 | 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".