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

Abstract

One of the biggest mysteries in neurobiology concerns the mechanisms responsible for the diversification of the brain over different time scales i.e. during development and evolution. Subtle differences 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 single organism, altered timing of developmental events can lead to individual variability, as well as malformation and disease. At the level of phylogeny, there are known interspecies differences in the timing of developmental events, and this is thought to be an important factor that drives phenotypic variation across evolution, known as heterochrony. A particularly striking example of phenotypic variation is the evolution of human cognitive abilities, which has largely been attributed to the development of the mammalian-specific neocortex and its subsequent expansion in higher primates. Here, I review how the timing of different aspects of cortical development specifies developmental outcomes within species, including processes of cell proliferation and differentiation, 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 knowledge with known differences in timing across species, timing changes that may have occurred during evolution are identified, which perhaps drove the phylogenetic diversification of neocortical structure and function.

Evo-devo dynamics of hominin brain size

“…The model provides insight into further debated questions. Variation in the timing of brain development at molecular, cellular, and histological levels has been proposed to lead to evolution of brain diversity [80][81][82] . Our results are consistent with these views.…”

Polycomb Repressive Complex 2 is critical for mouse cortical glutamatergic neuron development

“…Premature differentiation of neural progenitor cells is known to contribute to microcephaly, and to preferentially affect late born neurons within the cerebral cortex 36 . To investigate lamination in our model, we performed immunofluorescent staining of the neuronal markers Satb2, Ctip2, and Foxp2 (Figure 2A-I).…”

Evolution of cortical neurons supporting human cognition

“…We also acknowledge that evolutionary changes in the developmental timing of cortical neurons and synapses play an important role in the evolution of human cognition. Although this topic falls outside the scope of this review, we would like to point the reader to excellent recent reviews [24][25][26]. Finally, the focus of our review is on the pyramidal neurons of supragranular layers, as the morpho-electric properties of these neurons are more extensively studied in human cortex compared with deeper layers.…”