Pal_2025_Neurogenetics_26_48

Autism Spectrum Disorder, a complex neurodevelopmental disorder, is manifested by deficits in social communication and restricted, repetitive patterns of behavior, interests, or activities. Its molecular mechanism of pathology is not that much understood, though various genetic mutations have been established in its causation. The most important genes are Shank3, Cntnap2, Neuroligin3, and Arid1b. Recently, zebrafish (Danio rerio) have emerged as a highly valuable model organism to study these genetic contributions to ASD, given their genetic tractability, transparent embryos, and ease of behavioral assessment. This review discusses the models of zebrafish used to examine the roles of Shank3, Cntnap2, Neuroligin3, and Arid1b in synaptic function, neuronal connectivity, and behavioral abnormalities characteristic of ASD. We discuss the molecular pathways affected by mutations in these genes, including synapse formation, excitatory/inhibitory balance, and neuronal signaling, which lead to the neurodevelopmental impairments observed in ASD. We have also highlighted the various behavioral assays in zebrafish, such as social interaction tests, sensory processing assays, and repetitive behavior measurements, which are used to study ASD-like phenotypes. The unique advantages of zebrafish include high-throughput potential, the ability to monitor real-time neuronal activity, and the ease with which genetic manipulations can be done. The review focuses on the advancement of zebrafish in understanding ASD and their potential for rising targeted interventions to address core symptoms of the disorder.