Transcriptomics and functional genomics implicate WNT3 in hemispheric lateralization of speech production

Human speech and language depend on hemispheric specialization across cortical regions and cortico-striatal circuits. We profiled 125 human cortical samples from 13 Brodmann areas (BAs), bilaterally, across five donors to generate a hemisphere-resolved transcriptomic atlas and quantify region-specific lateralization. Integrating genome-wide association signals for speech-, language-, and reading-related traits with brain <i>cis</i>-expression quantitative trait loci (eQTL) and enhancer maps prioritized a regulatory axis linking rs62060948 to MYC binding and WNT3 expression. WNT3 was higher in right BA44 than left, and cellular assays supported MYC occupancy and showed reduced WNT3 after MYC knockdown. In mice, unilateral Wnt3 overexpression (<i>Wnt3</i> OE) in the dorsal striatum selectively altered ultrasonic vocalizations (USVs), locomotor activity, and myelin basic protein expression. These results connect regulatory variation to lateralized gene control and circuit function relevant to vocal communication, and provide a multiregional resource to support mechanistic studies in human tissue and animal models.