Molecular and cellular evolution of the primate dorsolateral prefrontal cortex

Area of Science:

• Neuroscience
• Evolutionary Biology
• Genomics

Background:

• The granular dorsolateral prefrontal cortex (dlPFC) is a key brain region for cognition, particularly in primates.
• Understanding dlPFC evolution requires detailed cellular and molecular comparisons across species.

Purpose of the Study:

• To comprehensively survey the cellular repertoire of the dlPFC in adult humans, chimpanzees, macaques, and marmosets.
• To identify conserved and divergent cellular subtypes and molecular features across these primate species.
• To investigate species-specific molecular differences, including gene expression patterns in neurons and glial cells.

Main Methods:

• Single-nucleus RNA sequencing (snRNA-seq) was performed on over 600,000 cells from the dlPFC of four primate species.
• Transcriptomic data were analyzed to define cell subtypes and compare molecular profiles across species.
• Specific genes, including somatostatin, tyrosine hydroxylase, and FOXP2, were examined for species-specific expression patterns.

Main Results:

• Most dlPFC cell subtypes are conserved across the studied primate species.
• Several cell subtypes were found to be species-specific.
• Substantial molecular differences were observed in homologous neuronal, glial, and non-neural cell subtypes, including human-specific expression of somatostatin and tyrosine hydroxylase, and human-specific FOXP2 expression in microglia.

Conclusions:

• The dlPFC cellular repertoire shows both conservation and divergence across anthropoid primates.
• Species-specific molecular differences in dlPFC cells likely contribute to cognitive specializations.
• This study provides a foundational resource for understanding the evolution of primate cognition and brain disorders.