The role of the IgSF9 transmembrane protein borderless in regulating axonal transport of presynaptic components in «Drosophila»
Bibliographic record
Abstract
Normal brain function requires proper targeting of synaptic vesicle (SV) and active zone (AZ) components for presynaptic assembly and function.Whether and how synaptogenic signals (e.g.adhesion) at axo-dendritic contact sites promote axonal transport of presynaptic components for synapse formation, however, remain unclear.The first section of my thesis work reveals that Borderless (Bdl), a member of the conserved IgSF9-family of trans-synaptic cell adhesion molecules, plays a novel and specific role in regulating axonal transport of SV components.Loss of bdl disrupts axonal transport of SV components in photoreceptor R8 axons.Genetic mosaic analysis, transgene rescue and cell-type-specific knockdown indicate that Bdl is required both preand postsynaptically for delivering SV components in R8 axons.Consistent with a role for Bdl in R8 axons, loss of bdl causes a failure of R8-dependent phototaxis response to green light.bdl interacts genetically with imac encoding for a member of the Unc-104/Imac/KIF1A-family motor proteins, and is required for proper localization of Imac in R8 presynaptic terminals.In the second part of my thesis, I show that loss of Neuroligin-2 (Dnlg2), another trans-synaptic adhesion molecule, induces a bdl-like SV phenotype in R8 axons.The results from biochemical and cell biology experiments suggest that Bdl and Dnlg2 physically interact in cis through the Bdl extracellular domain.Consistent with this observation, expression of a truncated Bdl protein lacking the cytoplasmic domain is sufficient to rescue the R8 SV mislocalization phenotype.Like bdl, dnlg2 interacts genetically with imac, suggesting a role for Dnlg2 in the Bdl-dependent pathway to mediate Imac activation.My thesis work supports a model in which Bdl and Dnlg2 function together in mediating specific axo-dendritic interactions, which up-regulates the Imac motor in promoting axonal transport of SV components for R8 presynaptic assembly and function.Here I would like to acknowledge all the individuals who have helped me throughout the progress of this work.There are so many people to thank and limited space, so I apologize in advance for those I have omitted.First and foremost, I would like to thank my supervisor, Dr. Yong Rao, for giving me the opportunity to work on these projects in his lab and his guidance throughout my doctoral studies.His mentorship and approach to science allowed me to hone my research and critical thinking abilities, while his intellect, patience, and understanding set an example all educators should strive for.
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 | 0.000 |
| 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".