The cellular and molecular basis of gyrus-sulcus specialization in the primate brain

Gyri and sulci are key anatomical features of the primate cerebral cortex, distinguished by their structural and functional specialization, yet their cellular and molecular foundations remain poorly understood. Here we utilized single-cell spatial transcriptomics data from adult male macaque monkey brains and developed gsModel, a customized deep learning framework that distinguishes sulci from gyri. Relying solely on local cell-type composition, gsModel achieved over 90% accuracy in the classification task, outperforming alternative machine learning models and predictors based on anatomical features. By integrative analysis with diffusion MRI tractography, we found that these compositional distinctions align with systematic variations in structural connectivity, linking local molecular architecture to macroscale wiring. Embedding-guided analyses further revealed key cell types and marker genes contributing to sulcus-gyrus differences, highlighting prominent contributions from upper-layer glutamatergic neurons and oligodendrocytes, as well as distinct gene regulatory networks underlying their expression profiles. Together, this work establishes a molecular framework linking microscale molecular architecture to macroscale cortical organization, providing a basis for mechanistic studies of region-specific structural and functional specialization in the primate cortex. This study uncovers how differences in brain cell composition help define cortical folds and reveals a link between microscopic cellular organization and large-scale brain networks in primates.