Role and Impact of the brsk2 Gene in Zebrafish Retinal Development and Visual Function Characterized by Behavioral, Histological, and Transcriptomic Analyses

Vision is fundamental to the acquisition of motor, cognitive, and social skills, playing a crucial role in typical development. Early visual impairments are associated with various neurodevelopmental conditions, including Autism Spectrum Disorder (ASD). The (Brain-specific serine/threonine-protein kinase 2, BRSK2) gene has been identified as a high-risk gene for ASD. This study aims to investigate the role of brsk2 in retinal photoreceptor development and visual function in zebrafish. Using behavioral assays, histological analysis, and transcriptomic profiling, we assessed the impact of brsk2 deletion on retinal structure and function. The results showed that brsk2ab−/− zebrafish larvae exhibited significantly enhanced light perception compared to wild-type (WT) controls. Structural analysis of the retina revealed disruptions in the layered organization, along with up-regulated rhodopsin expression in retinal cells. Additionally, transcriptomic analysis indicated that key opsins and genes involved in visual development and phototransduction pathways were markedly up-regulated following brsk2 deletion. This research highlights the importance of brsk2 in early retinal circuit development and its potential implications for understanding sensory processing deficits in neurodevelopmental disorders. By linking BRSK2 to specific sensory phenotypes, this study addresses a critical gap in knowledge regarding the mechanisms underlying sensory abnormalities in ASD and related conditions.