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

Zixian Wang1,2, Yanxi Chen3, Yongqi Feng4

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This study reveals a genetic link between vocal communication traits and brain gene expression. Researchers identified a regulatory pathway influencing WNT3 expression, crucial for hemispheric specialization in speech and language.

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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.