Opera Medica et Physiologica

Maayan Karlinski

Unfolding the Folds: How the Biomechanics of the Extracellular Matrix Contributes to Cortical Gyrification

The enlarged folded human cerebral cortex (CC) is considered a key feature for the complex cognitive and socioemotional behaviours man possesses. While structural, molecular and cellular suspects do exist, the underlying mechanisms involved in cortical gyrification in human, as compared to the lissencephalic brains (smooth brain) in rodents, are poorly understood (Fig. 1A). Such question withholds fundamental importance, as structural brain malformations are linked with a range of rare, yet devastating conditions.


The convoluted human cerebral cortex is one of the key features that allows for an increased neuronal density packing essential for the complex cognitive and socioemotional behaviours man possesses. Nevertheless, the underlying mechanisms involved in cortical folding remained a both intriguing and functionally important enigma. A crucial component known to be involved in the formation and maintenance of all tissues is the extracellular matrix (ECM), providing scaffolds which tie tissues and organs in place. The composition of the ECM in both developing and mature structures is constantly remodelled, degraded and secreted by numerous types of cells, and its role as a source of growth factors and signalling in morphogenesis, migration, and proliferation is increasingly appreciated. Evidence for the differential expression of ECM during gyrification pinpoints its potentially fundamental role in shaping the folds of the cerebral cortex through both mechanical and molecular configurations. This review aims at addressing key ideas, potential directions and discoveries that highlight biomechanics of the ECM during the construction of the cortex cerebral gyrification. 

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