Additive effects on craniofacial development upon conditional ablation of <scp>PDGFRα</scp> and <scp>SHP2</scp> in the mouse neural crest lineage
Bibliographic record
Abstract
Abstract Background Activity of the receptor tyrosine kinase PDGFRα and the tyrosine phosphatase SHP2 is critical for vertebrate craniofacial development. SHP2 has been shown to both positively and negatively regulate PDGFR signaling through the recruitment of Grb2 and dephosphorylation of the receptor, respectively. We sought to determine the effect of SHP2 binding to PDGFRα in the facial mesenchyme via phenotypic and biochemical analyses of an allelic series of mouse embryos with combined loss of both proteins in the neural crest lineage. Results We demonstrated that SHP2 preferentially binds PDGFRα /α homodimers among the three PDGFR dimers. We showed that double‐homozygous mutant embryos exhibit a combination, but not an improvement or worsening, of the phenotypes observed upon conditional ablation of PDGFRα or SHP2 in the neural crest lineage. We further revealed that cell death in the lateral nasal and maxillary processes underlies the upper jaw phenotypes in embryos with loss of SHP2 . Finally, we showed that E10 .5 Pdgfra +/fl ;Shp2 fl/fl ;Wnt1‐Cre +/Tg embryos have increased phosphorylation of PDGFRα and the downstream effector Erk1/2 compared to control and double‐heterozygous embryos. Conclusions We propose a putative model in which SHP2 binds and dephosphorylates PDGFRα while simultaneously increasing survival through an Erk1/2‐independent mechanism.
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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) | 0.001 | 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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".