Neuropilin 1 (NRP1) conveys SEMA3A signals to restrict physiological angiogenesis
Bibliographic record
Abstract
The class 3 semaphorin SEMA3A is a secreted glycoprotein that serves as an evolutionary conserved axon repellent with proposed vascular functions. In mice, SEMA3A is dispensable for developmental brain, limb or trunk blood vessel patterning, but restricts vessel branching in the zebrafish embryo trunk. Whereas neuropilin 1 (NRP1) is thought to be the SEMA3A receptor in the mouse, prior reports identified Plexin D1 as the Sema3a receptor in zebrafish trunk vessel patterning, with previous knockdown and knockout studies yielding contradictory results on Nrp1 requirement for vessel patterning in zebrafish. To resolve these discrepancies, we have refined the prior knockdown strategy to limit off target effects and generated mutant zebrafish embryos lacking both Nrp1a and Nrp1b paralogues to show that Nrp1 restricts trunk vessel patterning in a Sema3a-dependent manner. In agreement, we found that NRP1 is required in human endothelial cells for SEMA3A-induced repulsion. Moreover, we show that SEMA3A action via NRP1 does not involve the splicing regulation of FLT1, previously proposed to act downstream of Plexin D1. Instead, sustained NRP1 activation independent of SEMA3A increases the expression of the anti-angiogenic soluble FLT1 (sFLT1), establishing a feedback mechanism to limit endothelial proliferation. Together, these findings demonstrate a dual role for NRP1 in shaping physiological vascular morphogenesis. Thus, NRP1 mediates repulsive SEMA3A cues in endothelial cells, in analogy to its role in axon guidance, and further restricts angiogenesis by promoting the release of sFLT1 in a SEMA3A-independent manner.
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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) | 0.008 | 0.003 |
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".