Cyclic adenosine monophosphate and rho guanine triphosphatase signaling in the guidance of axons to netrin-1
Bibliographic record
Abstract
The adult nervous system is a network of neurons connected to each other by thin processes, called axons. During development, axons are guided to their targets by patterned chemical cues. The leading tip of an axon, called the growth cone, pulls the axon to its target with cell surface receptors that sense these cues and trigger biochemical cascades which extend, retract or turn the axon. This thesis examines mechanisms involved in the guidance of axons to the cue netrin-1. I test the hypothesis that netrin-1 may function as an adhesive ligand. As well, I examine the role of two signaling pathways, the cyclic adenosine monophosphate (cAMP) and the rho guanine triphosphatase (Rho GTPase), in the guidance of axons to netrin-1. I report that neurons efficiently attach to netrin-1 and that their growth cones display morphological changes consistent with its function as an adhesive ligand. Inhibition of the RhoA subfamily of Rho GTPases or elevation of cAMP levels increases the plasma membrane presentation of netrin-1's receptor DCC and promotes axon outgrowth and turning to netrin-1. This observation is consistent with the possibility that these two biochemical pathways are linked. However, an important difference exists in how these pathways are regulated by netrin-1; while netrin-1 inhibits RhoA activation, it does not affect cAMP levels. Studies by others have reported that inhibiting RhoA activity or elevating cAMP concentration promotes axon regeneration following injury. These studies did not, however, examine the axon's guidance decisions past the injury site; while overcoming an inhibitory injury site likely involves ignoring or switching the response to inhibitory cues, guidance to their appropriate targets requires axons to sense and respond appropriately to the cues in their environment. Results presented here indicate that inhibiting RhoA or augmenting cAMP levels promote axonal attraction to the netrin-1 guidance cue.
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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 | 0.001 | 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".