Expansion of the neocortex is thought to underpin the higher cognitive abilities of a number of mammalian lineages, such as cetaceans, elephants, and primates, with humans exhibiting a particularly enlarged and dense cerebral cortex. However, the evolutionary and developmental mechanisms that led to this expansion are not well-understood and limited to correlative observations. Historically, this has been due to technical and ethical limitations owing to the intractability of various species for functional studies. Nonetheless, comparative neuroanatomical observations have revealed probable cell-biological mechanisms that may have driven reorganization of neocortical architecture and cortical expansion. Furthermore, new in vitro neural differentiation technologies are allowing, for the first time, functional studies to test existing hypotheses and identify new mechanisms. Here, we introduce three-dimensional neural organoids as a powerful new tool for these types of evolutionary-neurodevelopmental studies.
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