A SnoN–Ccd1 Pathway Promotes Axonal Morphogenesis in the Mammalian Brain
Bibliographic record
Abstract
The transcriptional corepressor SnoN is a critical regulator of axonal morphogenesis, but how SnoN drives axonal growth is unknown. Here, we report that gene-profiling analyses in cerebellar granule neurons reveal that the large majority of genes altered upon SnoN knockdown are surprisingly downregulated, suggesting that SnoN may activate transcription in neurons. Accordingly, we find that the transcriptional coactivator p300 interacts with SnoN, and p300 plays a critical role in SnoN-induced axon growth. We also identify the gene encoding the signaling scaffold protein Ccd1 as a critical target of SnoN in neurons. Ccd1 localizes to the actin cytoskeleton, is enriched at axon terminals in neurons, and activates the axon growth-promoting kinase JNK (c-Jun N-terminal protein kinase). Knockdown of Ccd1 in neurons reduces axonal length and suppresses the ability of SnoN to promote axonal growth. Importantly, Ccd1 knockdown in rat pups profoundly impairs the formation of granule neuron parallel fiber axons in the rat cerebellar cortex in vivo. These findings define a novel SnoN-Ccd1 link that promotes axonal growth in the mammalian brain, with important implications for axonal development and regeneration.
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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 | 0.000 |
| 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".