Mechanical stress connects cortical folding to fiber organization in the developing brain

During development of the gyrencephalic brain, both the formation of cortical folds and the establishment of axonal tracts require large, coordinated mechanical deformations. Cortical folding enables a high ratio of cortical surface area to brain volume, which is thought to enhance overall processing power. Meanwhile, a complex network of axonal connections facilitates communication between distant brain regions. The mechanisms underlying the formation of brain folds and axon tract organization remain widely debated. However, evidence emerging from measurements of mechanical stress, combined with physical and mathematical models, suggests that constrained cortical expansion generates folds via mechanical instability. In this opinion article, we highlight recent models and experimental data suggesting that mechanical stress induced by cortical folding also mediates axonal growth. We propose a key role for mechanics in establishing brain morphology and the organization of white matter fascicles of the mature brain.