The oxidizing enzyme CYP26a1 tightly regulates the availability of retinoic acid in the gastrulating mouse embryo to ensure proper head development and vasculogenesis
Bibliographic record
Abstract
Retinoic acid (RA) has been implicated as one of the signals providing a posterior character to the developing vertebrate central nervous system. Embryonic RA first appears in the posterior region of the gastrulating embryo up to the node level, where it may signal within the adjacent epiblast and/or newly induced neural plate to induce a hindbrain and spinal cord fate. Conversely, rostral head development requires forebrain-inducing signals produced by the anterior visceral endoderm and/or prechordal mesoderm, and there is evidence that RA receptors must be in an unliganded state to ensure proper head development. As RA is a diffusible lipophilic molecule, some mechanism(s) must therefore have evolved to prevent activation of RA targets in anterior regions of the embryo. This might result from RA catabolism mediated by the CYP26A1 oxidizing enzyme, which is transiently expressed in anteriormost embryonic tissues; however, previous analysis of Cyp26a1(-/-) mouse mutants did not clearly support this hypothesis. Here we show that Cyp26a1(-/-) null mutants undergo head truncations when exposed to maternally-derived RA, at doses that do not affect wild-type head development. These anomalies are linked to a widespread ectopic RA signaling activity in rostral head tissues of CYP26A1-deficient embryos. Thus, CYP26A1 is required in the anterior region of the gastrulating mouse embryo to prevent teratological effects that may result from RA signaling. We also report a novel role of CYP26A1 during early development of the intra- and extra-embryonic vascular networks.
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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 | 0.001 |
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 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".