Consolidation of cell-ECM adhesion through direct talin-mediated actin linkage is essential for mouse embryonic morphogenesis
Bibliographic record
Abstract
During animal development, cell-ECM adhesion mediated by integrins is required for the assembly and maintenance of tissues and organs. It can either be transient or stable and requires linking integrins to the cytoskeleton. Talin can link integrins to actin either directly through its actin-binding sites (ABSs) or indirectly by recruiting downstream actin-binding molecules. In Drosophila, talin's ABS3 domain is essential for biological functions, but its role remains unknown in mammalian systems. Here, we investigate the role of direct talin-mediated actin linkage in mammals by generating a mouse model containing point mutations in talin's ABS3 domain. We find that mutant mice exhibit early developmental defects and die midway through embryogenesis. Primary mouse embryonic fibroblasts generated from mutants form prominent focal adhesions but show defective consolidation and maturation. Adhesion dynamics, cell spreading, actin dynamics and organization, and traction force generation are also impacted in mutants, which affect processes such as cell migration that impinge on multiple events during early mouse embryogenesis. Overall, our work provides key mechanistic insights into how direct coupling of ECM to actin through talin has specific and critical roles in controlling adhesion dynamics required for early mammalian development.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".