Deconstructing cortical folding: genetic, cellular and mechanical determinants

Folding of the cerebral cortex is a fundamental milestone of mammalian brain evolution and is associated with dramatic increases in size and complexity. New animal models, genetic tools and bioengineering materials have moved the study of cortical folding from simple phenomenological observation to sophisticated experimental testing. Here, we provide an overview of how genetics, cell biology and biomechanics shape this complex and multifaceted process and affect each other. We discuss the evolution of cortical folding and the genomic changes in the primate lineage that seem to be responsible for the advent of larger brains and cortical folding. Emerging technologies now provide unprecedented tools to analyse and manipulate cortical folding, with the promise of elucidating the mechanisms underlying the stereotyped folding of the cerebral cortex in its full complexity.