Cortical folding patterns are encoded in the geometry of the unfolded neocortex.

Abstract

Cortical folding patterns are conserved across individuals of gyrencephalic species and are closely related to cytoarchitectural organisation, connectivity, and function. Early morphogen gradients have been proposed as the molecular source of positional information encoding these patterns - a gyral molecular protomap - but the contribution of neocortical geometry to this encoding has not been examined. Here we show that the geometry of the unfolded ferret brain guides the adult folding pattern before any folding has occurred. Using high-resolution MRI surface reconstructions from postnatal day (P) 0 to adults, we demonstrate that newborn neocortical curvature predicts mature curvature maps, sulcal-gyral fate, and fold orientation. Pre-folding curvature correlates with expression of key patterning genes, and a mediation analysis indicates that geometry at P0 is the principal predictor of sulcal-gyral fate at P6. Mechanical simulations show that regions of high curvature act as autonomous anchors that organise the folding pattern. These results suggest that neocortical geometry constitutes a form of positional information that complements molecular patterns in regulating cortical organisation, and that a complete account of cortical development requires the integration of geometric and mechanical processes alongside molecular signalling.