Inside–out integrin activation is essential for early mammalian development
Bibliographic record
Abstract
The attachment of cells to the extracellular matrix (ECM) is essential for morphogenesis. The activity of Integrins, the main mediators of cell-ECM adhesion in animals, is required for morphogenesis and must be precisely regulated to ensure proper development. However, the mechanisms that ensure precise integrin activity during animal development are poorly understood. The best characterized mechanism for integrin regulation is conformational change driven by either extracellular signals ("outside-in activation") or by intracellular signals ("inside-out activation"). The cytoplasmic protein talin is a key regulator of inside-out activation. We used mutations in talin to demonstrate, for the first time, that modulation of integrin activation is essential for early mammalian development. We find that integrin activation mutants die by E8.5-E9.5 and show developmental delay and abnormal growth. Intriguingly, disrupting integrin regulation does not impinge on embryonic patterning and ECM distribution. Analysis of embryonic stem cells isolated from integrin activation mutants revealed a reduction in the strength of cell-ECM attachment but only mild defects in focal adhesion number and maturation. Notably, activation mutants at E7.5 showed increased cell death and reduced cell-proliferation Overall, we find that inside-out integrin activation strengthens cell-ECM attachment in early mouse development that is essential for cell survival and proliferation.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".