Bidirectional transfer of a small membrane-impermeable molecule between the Caenorhabditis elegans intestine and germline
Bibliographic record
Abstract
The extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) is a positive regulator of cell proliferation often upregulated in cancer. Its Caenorhabditis elegans ortholog MPK-1 stimulates germline stem cell (GSC) proliferation nonautonomously from the intestine or somatic gonad. How MPK-1 can perform this task from either of these two tissues however remains unclear. We reasoned that somatic MPK-1 activity could lead to the generation of proproliferative small molecules that could transfer from the intestine and/or somatic gonad to the germline. Here, in support of this hypothesis, we demonstrate that a significant fraction of the small membrane-impermeable fluorescent molecule, 5-carboxyfluorescein, transfers to the germline after its microinjection in the animal's intestine. The larger part of this transfer targets oocytes and requires the germline receptor mediated endocytosis 2 (RME-2) yolk receptor. A minor quantity of the dye is however distributed independently from RME-2 and more widely in the animal, including the distal germline, gonadal sheath, coelomocytes, and hypodermis. We further show that the intestine-to-germline transfer efficiency of this RME-2 independent fraction does not vary together with GSC proliferation rates or MPK-1 activity. Therefore, if germline proliferation was influenced by small membrane-impermeable molecules generated in the intestine, it is unlikely that proliferation would be regulated at the level of molecule transfer rate. Finally, we show that conversely, a similar fraction of germline injected 5-carboxyfluorescein transfers to the intestine, demonstrating transfer bidirectionality. Altogether, our results establish the possibility of an intestine-to-germline signaling axis mediated by small membrane-impermeable molecules that could promote GSC proliferation cell nonautonomously downstream of MPK-1 activity.
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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".