CDH-3/cadherin, YAP-1/YAP, and EGL-44/TEAD promote SYX-2/syntaxin and EFF-1 fusogen-mediated phagosome closure
Bibliographic record
Abstract
Physical interactions between cells can profoundly impact cell fate. A vital cell fate for normal development and homeostasis is programmed cell death. Cells fated to die must be efficiently cleared via phagocytosis, with defects associated with a variety of diseases. How cell-cell physical associations affect programmed cell elimination is not fully understood. Here we describe, in vivo, a cell-cell adhesion-driven signaling pathway that ensures compartment-specific cell clearance. We previously described the specialized cell death program "Compartmentalized Cell Elimination" (CCE) in the Caenorhabditis elegans embryo. During CCE, the tail-spike scaffolding cell (TSC), a polarized epithelial cell with a posteriorly directed process, is eliminated via an ordered death sequence. The TSC scaffolds the tail tip, formed by the hyp10 epithelial cell, which in turn serves as the phagocyte for the dying TSC process. We have previously provided mechanistic insights into the poorly understood step of phagocytosis, phagosome sealing, reporting that the fusogen EFF-1 helps clear the TSC process specifically. We identify here a genetic pathway that promotes the translocation of EFF-1 to sealing sites. We identify an upstream role for cell-cell physical association and signaling via the cadherin CDH-3, followed by new roles for the transcription factors YES-associated protein (YAP)-1/YAP and EGL-44/TEAD in promoting the localization of SYX-2/syntaxin around the dying TSC remnant. Moreover, we find that SYX-2, known to promote EFF-1's role in wound healing, also promotes EFF-1 translocation to sites of phagosome closure. Our work sheds additional light on phagosome sealing and implicates cell-cell adhesive forces and signaling as important in cell uptake.
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How this classification was reachedexpand
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 | 0.000 | 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) | 0.000 | 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 teacher head, 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".