Dissection of Semaphorin reverse signaling in axon guidance
Bibliographic record
Abstract
My PhD thesis describes original study in the guidance of photoreceptor (R-cell) axons in the developing Drosophila visual system. I investigate the role of the transmembrane protein Semaphorin1a (Sema1a) and PlexinA (PlexA) in R-cell axon guidance and dissect the Sema1a reverse signaling pathway. My results indicate that Sema1a functions as a receptor to mediate an attractive response in the Drosophila visual system, and PlexA acts as the upstream regulator of Sema1a.Semaphorins belong to a large family of both secreted and transmembrane proteins known as axon guidance molecules in vertebrates and invertebrates. Drosophila Sema1a is a transmembrane protein. Previous studies have shown that Sema1a functions as the ligand of its receptor PlexA together with Otk inducing a repulsive signaling pathway in the Drosophila neuromuscular system. However, whether it is the case in the Drosophila visual system remains unknown. Our results revealed that sema1a is required in R1-R6 axons for their association and guidance to form a proper topographic termination layer. The function of sema1a in R cells is cell-autonomous. Overexpression of sema1a causes a hyper-fasciculation phenotype in which abnormal thicker bundles are formed in both lamina and medulla. Interestingly, we found that the cytoplasmic domain of Sema1a is required for its function in R-cell axon guidance. All these results suggest that Sema1a functions as an attractive receptor to mediate R-cell interactions during R-cell axon projections, which is totally different with previous studies.Furthermore, I investigate the upstream ligand of Sema1a in our model by testing candidate-gene approach. I found that plexA displays a sema1a-like loss-of-function and gain-of-function phenotype in the Drosophila visual system. In addition, plexA genetically interacts with sema1a. These results indicate that plexA and sema1a function in the same signaling pathway. Interestingly, the cytoplasmic domain of PlexA is dispensable for its function in inducing the hyper-fasciculation phenotype in R-cell axon guidance, suggesting that PlexA functions as a ligand. Epistasis analysis suggests that plexA functions as an upstream regulator of sema1a. Taken all together, we propose that PlexA functions as the ligand of Sema1a in the Sema1a reverse signaling pathway in the Drosophila visual system.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.003 | 0.001 |
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".