Timing as a Mechanism of Development and Evolution in the Cerebral Cortex

One of the biggest mysteries in neurobiology concerns the mechanisms responsible for thediversification of the brain over different time scales i.e. during development and evolution. Subtledifferences in the timing of biological processes during development, e.g. onset, offset, duration,speed and sequence, can trigger large changes in phenotypic outcomes. At the level of a singleorganism, altered timing of developmental events can lead to individual variability, as well asmalformation and disease. At the level of phylogeny, there are known interspecies differences inthe timing of developmental events, and this is thought to be an important factor that drivesphenotypic variation across evolution, known as heterochrony. A particularly striking example ofphenotypic variation is the evolution of human cognitive abilities, which has largely been attributedto the development of the mammalian-specific neocortex and its subsequent expansion in higherprimates. Here, I review how the timing of different aspects of cortical development specifiesdevelopmental outcomes within species, including processes of cell proliferation anddifferentiation, neuronal migration and lamination, and axonal targeting and circuit maturation.Some examples of the ways that different processes might “keep time” in the cortex are explored,reviewing potential cell-intrinsic and -extrinsic mechanisms. Further, by combining this knowledgewith known differences in timing across species, timing changes that may have occurred duringevolution are identified, which perhaps drove the phylogenetic diversification of neocorticalstructure and function.