Bridging the anatomical gap: evolutionary conservation of genetic mechanisms in corpus callosum disorders across human, mouse, and zebrafish

The Corpus Callosum (CC) is the largest white matter structure in the placental mammalian brain, facilitating critical interhemispheric communication. Anomalies of the CC, ranging from complete agenesis (ACC) to hypoplasia and dysgenesis, are frequent manifestations of complex neurodevelopmental syndromes. While mouse has historically served as the primary model for these disorders due to its conserved mammalian neuroanatomy, zebrafish has emerged as a powerful, albeit non-mammalian, alternative. This review synthesizes data from human, mouse, and zebrafish genetic tables to highlight the anomalies occurring at distinct steps of CC development. We examine how mouse models have been instrumental in mapping the structural failures of commissure formation. Furthermore, we address the utility of zebrafish models demonstrating that they effectively model the underlying cellular mechanisms of these disorders. Through an analysis of convergent phenotypes and divergent phenotypic readouts, we state that zebrafish provide a complementary platform for dissecting the molecular etiology of human callosal disorders.