Mechanisms of RhoA inactivation and CDC42 and Rac1 activation during zebrafish optic nerve regeneration
Bibliographic record
Abstract
When axons of the mammalian central nervous system (CNS) are injured, they fail to regenerate, while those of lower vertebrates undergo regeneration after injury. Wingless-type MMTV integration site family (Wnt) proteins play important roles in the CNS, and are reported to be activated after mammalian spinal cord or brain injury. Moreover, for axon growth to proceed, it is thought that small G-proteins, such as CDC42 and Rac1, need to be activated, whereas RhoA must be inactivated. However, the cell and molecular mechanisms involved in optic nerve regeneration remain unclear. In this study, we investigated axonal regeneration after injury using the zebrafish optic nerve as a model system. We sought to clarify the role of Wnt proteins and the mechanisms involved in the activation and inactivation of small G-proteins in nerve regeneration. After optic nerve injury, mRNA levels of Wnt5b, TAX1BP3 and ICAT increased in the retina, while those of Wnt10a decreased. These changes were associated with a reduction in β-catenin in nuclei. We found that Wnt5b activated CDC42 and Rac1, leading to the inactivation of RhoA, which appeared to be dependent on increased TAX1BP3 mRNA levels. Furthermore, we found that mRNA levels of Daam1a and ARHGEF16 decreased. We speculate that the decrease in β-catenin levels, which also further reduces levels of active RhoA, might contribute to regeneration in the zebrafish. Collectively, our novel results suggest that Wnt5b, Wnt10a, ICAT and TAX1BP3 participate in the activation and inactivation of small G-proteins, such as CDC42, Rac1 and RhoA, during the early stage of optic nerve regeneration in the zebrafish.
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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 | 0.001 |
| 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 | 0.001 |
| 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".