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

## TL;DR

The study finds that the WNT3 gene is linked to brain lateralization in speech production, with higher expression in the right hemisphere and effects on vocal communication in mice.

## Contribution

The paper identifies a regulatory axis involving rs62060948, MYC binding, and WNT3 expression that connects genetic variation to lateralized brain function in speech.

## Key findings

- WNT3 expression is higher in the right BA44 region of the human brain compared to the left.
- MYC knockdown reduces WNT3 expression, supporting MYC's regulatory role.
- Unilateral Wnt3 overexpression in mice affects vocalizations, locomotion, and myelin basic protein expression.

## Abstract

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 cis-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 (Wnt3 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.

•Hemisphere-resolved cortical transcriptomic atlas across 13 Brodmann areas•Hemisphere-dependent regional expression patterns revealed across human cortex•rs62060948 links MYC binding to right BA44 WNT3; MYC knockdown lowers WNT3•Left striatal Wnt3 alters mouse vocalizations, locomotion, and MBP expression

Hemisphere-resolved cortical transcriptomic atlas across 13 Brodmann areas

Hemisphere-dependent regional expression patterns revealed across human cortex

rs62060948 links MYC binding to right BA44 WNT3; MYC knockdown lowers WNT3

Left striatal Wnt3 alters mouse vocalizations, locomotion, and MBP expression

Audiology; Neuroscience; Sensory neuroscience; Genomics