The neocortical infrastructure for language involves region-specific patterns of laminar gene expression

Area of Science:

• Neuroscience
• Genomics
• Molecular Biology

Background:

• The human brain's language network involves the inferior frontal and temporal cortex, typically left-hemisphere dominant.
• Understanding the molecular basis of functional specialization and interconnectivity in this network is crucial.
• Cortical connections exhibit layer-specific organization.

Purpose of the Study:

• To investigate layer-specific gene expression differences between frontal and temporal language regions.
• To identify genes with distinct laminar expression profiles in the language network.
• To explore the association of these genes with brain connectivity and language-related disorders.

Main Methods:

• Spatial transcriptomics was used on postmortem human cortical tissue from language network regions.
• Gene expression data were analyzed across cortical layers.
• Integration with single-cell expression data identified differentially expressed genes.
• Genome-wide association studies (GWAS) were performed on identified genes.

Main Results:

• 56 genes showed differential laminar expression between frontal and temporal language cortex, with upregulation in specific excitatory neuron layers (II/III and/or V/VI).
• DNA variants in these 56 genes were associated with variations in structural connectivity between frontal and temporal language regions.
• These genetic variants also showed associations with dyslexia and schizophrenia, disorders often impacting language.

Conclusions:

• Region-specific patterns of laminar gene expression are a characteristic feature of the human brain's language network.
• These findings highlight a molecular basis for the functional organization of language processing.
• The identified genes provide potential targets for understanding and treating language-related neurological conditions.