Dlg5 and Cadherins are key to peripheral glia integrity
Bibliographic record
Abstract
ABSTRACT Glial cells in the peripheral nerve wrap axons to insulate them and ensure efficient conduction of neuronal signals. In the myelin sheath, it is proposed that the autotypic tight junctions and adherens junctions form glia-glia complexes that stabilize the glia sheath in myelinating glia. Yet the role of adhesion junctions in non-myelinating glia of vertebrates or invertebrates has not been clearly established. Many components of adhering junctions contain PDZ (PSD-95, Dlg, ZO1) domains or are recruited to these junctions by PDZ binding motifs. To test for the role of PDZ domain proteins in glial sheath formation, we carried out an RNAi screen using Drosophila melanogaster to knockdown each of the 66 predicted PDZ domain proteins in the peripheral glia. We identified six PDZ genes with potential roles in glial morphology, and further investigated Discs-large 5 (Dlg5), a scaffolding protein with no previously known function in glia. Knockdown of Dlg5 disrupts subperineurial glia (SPG) morphology, including gaps in the membrane that coincide with disruption of septate junction proteins. To further our investigation of Dlg5, we focused on cadherins and found both N-Cadherin and E-Cadherin are expressed throughout peripheral glia. Knockdown of E-Cadherin phenocopied the loss of Dlg5 leading to gaps in the SPG and septate junctions while only simultaneous loss of both N-Cadherins (NCad, and CadN2) had the same effect. The loss of all three Cadherins enhanced these phenotypes as did loss of Dlg5 when paired with cadherin knockdown. This leads to a model where Dlg5 plays a role in conjunction with cadherins in glial membrane stabilization and septate junction formation in the subperineurial glia.
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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".