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bioRxiv · 10.1101/2024.10.01.616190

Pannexin-2 deficient zebrafish develop ocular and visual motor behaviour defects

Shanbhag, R.·Zoidl, G. S. O.·Sabour, S.·Nakhuda, F.·Zoidl, C.·Bahl, A.·Tabatabaei, N.·Zoidl, G. R.
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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{Delta}11) 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{Delta}11 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{Delta}11 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{Delta}11 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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Shanbhag, R., Zoidl, G. S. O., Sabour, S., Nakhuda, F., Zoidl, C., Bahl, A., Tabatabaei, N., Zoidl, G. R.. 2024-10-03. Pannexin-2 deficient zebrafish develop ocular and visual motor behaviour defects. https://doi.org/10.1101/2024.10.01.616190

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