The Aplnr GPCR regulates myocardial progenitor development via a novel cell-non-autonomous, Gαi/o protein-independent pathway
Why this work is in the frame
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Bibliographic record
Abstract
Myocardial progenitor development involves the migration of cells to the anterior lateral plate mesoderm (ALPM) where they are exposed to the necessary signals for heart development to proceed. Whether the arrival of cells to this location is sufficient, or whether earlier signaling events are required, for progenitor development is poorly understood. Here we demonstrate that in the absence of Aplnr signaling, cells fail to migrate to the heart-forming region of the ALPM. Our work uncovers a previously uncharacterized cell-non-autonomous function for Aplnr signaling in cardiac development. Furthermore, we show that both the single known Aplnr ligand, Apelin, and the canonical Gα(i/o) proteins that signal downstream of Aplnr are dispensable for Aplnr function in the context of myocardial progenitor development. This novel Aplnr signal can be substituted for by activation of Gata5/Smarcd3 in myocardial progenitors, suggesting a novel mechanism for Aplnr signaling in the establishment of a niche required for the proper migration/development of myocardial progenitor cells.
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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 | 0.002 | 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 | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it