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

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Human speech and language rely on specialized brain regions and circuits.
• Understanding the genetic basis of hemispheric specialization is key to studying communication disorders.

Purpose of the Study:

• To create a hemisphere-resolved transcriptomic atlas of human cortical samples.
• To identify regulatory elements and genes involved in speech, language, and reading lateralization.

Main Methods:

• Profiling 125 human cortical samples from 13 Brodmann areas (BAs) bilaterally.
• Integrating genome-wide association study (GWAS) data with brain cis-expression quantitative trait loci (eQTL) and enhancer maps.
• Performing cellular assays and mouse models to validate findings.

Main Results:

• A regulatory axis was prioritized, linking rs62060948 to MYC binding and WNT3 expression.
• WNT3 expression was found to be higher in the right BA44 compared to the left.
• Unilateral Wnt3 overexpression in mice altered ultrasonic vocalizations and locomotor activity.

Conclusions:

• The study connects genetic variation to lateralized gene control and circuit function in vocal communication.
• Findings provide a valuable resource for mechanistic studies in human tissues and animal models.