Robinow Syndrome <i>DVL1</i> variants disrupt morphogenesis and appendage formation in a Drosophila disease model
Bibliographic record
Abstract
Abstract Robinow Syndrome is a rare developmental syndrome caused by variants in numerous genes involved in Wnt signaling pathways. We previously showed that expression of patient variants in Drosophila and a chicken model disrupts the balance of canonical and non-canonical/PCP Wnt signaling. We also noted neomorphic effects that warranted further investigation. In this study, we examine morphological changes that occur as a result of one variant, DVL1 1519 Δ T , that serves as a prototype for the other pathogenic variants. We show that epithelial imaginal disc development is disrupted in legs and wings. Shortened leg segments are reminiscent of shortened limb bones seen in RS patients. We find that imaginal disc development is disrupted and accompanied by increased cell death, without changes in cell proliferation. Furthermore, we find altered dynamics of basement membrane components and modulators. Notably we find increased MMP1 expression and tissue distortion, which is dependent on JNK signaling. We also find enhanced collagen IV (Viking) secreted from cells expressing DVL1 1519 Δ T . Through these studies we have gained more insight into developmental consequences of DVL1 variants implicated in autosomal dominant Robinow Syndrome.
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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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".