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This study demonstrates that the geometry of the smooth, unfolded neocortex in newborn ferrets predicts the adult brain's folding patterns before any folding occurs. Using MRI imaging from birth through adulthood, researchers found that curvature patterns present at birth correlate with later sulci and gyri locations, expression of key developmental genes, and final fold orientations. Mechanical simulations suggest that high-curvature regions act as structural anchors that organize subsequent folding, indicating that physical geometry works alongside molecular signals to determine cortical organization.
Why it matters
Understanding how brain folding patterns are established could provide insights into neurodevelopmental disorders associated with abnormal cortical folding, such as lissencephaly or polymicrogyria. This research suggests that cortical development involves an interplay between geometric, mechanical, and molecular processes, which may inform approaches to studying or potentially addressing developmental brain abnormalities.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
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.
Source: Cortical folding patterns are encoded in the geometry of the unfolded neocortex.