Pannexin-2 deficiency disrupts visual pathways and leads to ocular defects in zebrafish
Bibliographic record
Abstract
Abstract Pannexin-2 (Panx2) is a unique ion channel localized to ER-mitochondria contact sites. These dynamic and specialized microdomains are abundant in neurons and glia and essential for cellular signaling and metabolism. While synaptic interactions are well-studied, the role of intracellular contacts, such as those of ER-mitochondrial junctions, in neuronal function and neurodegeneration remains largely unexplored. To investigate the roles of Panx2 in neuronal communication, we meticulously examined its expression pattern in the zebrafish brain and used TALEN technology to generate homozygous Panx2 knockout ( Panx2 Δ11 ) zebrafish. Our results demonstrate that panx2 mRNA is present in several brain regions, notably in visual centers such as the optic tectum and the thalamus. In 6 days post fertilization TL ( Panx2 +/+ ) larvae, Panx2 expression was observed in the inner and outer plexiform layers of the retina and the arborization fields of the optic tract. Transcriptome profiling of Panx2 Δ11 larvae by RNA-seq analysis revealed down-regulation of vision-related genes, specifically those involved in visual and sensory perception and lens development. Behavioral tests showed that loss of Panx2 leads to an altered ability to interpret visual information, such as changes in ambient illuminations, and respond with the characteristic motor action. Panx2 Δ11 larvae exhibited reduced locomotor activity during light and increased activity during dark phases. Additionally, the knockout larvae displayed significantly impaired optomotor response (OMR). Lastly, when we tested the retinal structure of adult zebrafish eyes using optical coherence tomography (OCT), Panx2 Δ11 fish revealed a longer mean axial length and a negative shift in retinal refractive error (RRE) values; both indicative of myopia. Our findings highlight a distinct, novel function of Panx2 in retinal development, visual perception, and ocular health, beyond its recognized roles in neurodevelopment and tumor-suppressing properties in cancer cells.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 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".