Novel Retinoid Targets in the Mouse Limb during Organogenesis
Bibliographic record
Abstract
Bioactive retinoids are potent limb teratogens, upregulating apoptosis, decreasing chondrogenesis, and producing limb-reduction defects. To target the origins of these effects, we examined gene expression changes in the developing murine limb after 3 h of culture with teratogenic concentrations of vitamin A. Embryonic day 12 CD-1 limbs were cultured in the absence or presence of vitamin A (retinol acetate) at 1.25 and 62.5muM (n = 5). Total RNA was used to probe Atlas 1.2 cDNA arrays. Eighty-one genes were significantly upregulated by retinol exposure; among these were key limb development signaling molecules, extracellular matrix and adhesion proteins, oncogenes, and a large number of transcriptional regulators, including Eya2, Id3, Snail, and Hes1. To relate these expression changes to teratogenic outcome, the response of these four genes was assessed after culture with vitamin A and retinoid receptor antagonists that are able to rescue retinoid-induced malformations; expression levels were correlated with limb malformations. Lastly, pathways analysis revealed that a large number of the genes significantly affected by retinoid treatment are functionally linked through direct interactions. Several regulatory gene cascades emerged relevant to morphogenesis, cell-fate, and chondrogenesis; moreover, members of these cascades crosstalk with one other. These results indicate that retinoids act in a coordinated fashion to disrupt development at multiple levels. In sum, this work proposes several unifying mechanisms for retinoid-induced limb malformations, identifies novel retinoid targets, and highlights Eya2, Id3, Snail, and Hes1 as potential key teratogenic effectors.
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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 | 0.001 | 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 | 0.000 |
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".