# Zebrafish cdh23 Affects Rod Cell Phototransduction Through Regulating Ca2+ Transport and MAPK Signaling Pathway

## TL;DR

This study explores how mutations in the CDH23 gene affect vision by influencing calcium transport and the MAPK signaling pathway in zebrafish.

## Contribution

The study reveals a novel role of cdh23 in regulating Ca2+ and MAPK signaling in photoreceptor cells, linking it to vision impairment.

## Key findings

- cdh23−/− zebrafish showed increased cell death in the retina due to Ca2+ and MAPK signaling interactions.
- Transcriptomic analysis identified differentially expressed genes related to photoreceptor degeneration and the MAPK pathway.
- H&E staining showed no morphological differences in the cdh23−/− retina compared to controls.

## Abstract

Mutations in the pathogenic gene CDH23 are known to cause Usher syndrome, affecting both auditory and visual functions. Our previous results provided valuable insights into the mechanisms underlying congenital hearing loss associated with CDH23 mutations. However, the molecular mechanisms and signaling pathways that influence vision remain largely unknown. In this study, transcriptional sequencing and bioinformatics analysis were conducted to compare gene expression between the control and cdh23−/−. Additionally, RT-qPCR experiments were performed to further validate the bioinformatics analysis results. The comparative transcriptomic analysis identified differentially expressed genes associated with photoreceptor degeneration and the mitogen-activated protein kinase (MAPK) signaling pathway. Embryos were subjected to hematoxylin and eosin (H&E) staining to assess their histological changes. The results showed that the cdh23−/− retina was morphologically indistinguishable from the control. Apoptosis was assessed using TUNEL staining, which revealed an increase in total cell death in the cdh23−/− retina. Our results revealed that the cell death was induced by Ca2+ and MAPK signaling interactions following photoreceptor degeneration. This study provides insights into the mechanisms underlying the role of cdh23 in vision.