Area 10 is one of the cortical areas of the frontal lobe involved in higher cognitive functions such as the undertaking of initiatives and the planning of future actions. It is known to form the frontal pole of the macaque and human brain, but its presence and organization in the great and lesser apes remain unclear. It is here documented that area 10 also forms the frontal pole of chimpanzee, bonobo, orangutan, and gibbon brains. Imaging techniques and stereological tools are used to characterize this area across species and provide preliminary estimates of its absolute and relative size. Area 10 has similar cytoarchitectonic features in the hominoid brain, but aspects of its organization vary slightly across species, including the relative width of its cortical layers and the space available for connections. The cortex forming the frontal pole of the gorilla appears highly specialized, while area 10 in the gibbon occupies only the orbital sector of the frontal pole. Area 10 in the human brain is larger relative to the rest of the brain than it is in the apes, and its supragranular layers have more space available for connections with other higher-order association areas. This suggests that the neural substrates supporting cognitive functions associated with this part of the cortex enlarged and became specialized during hominid evolution.
The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (NOVA1) plays a key role in neural development and function. NOVA1 also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of NOVA1. Moreover, levels of synaptic markers and synaptic protein coassociations correlated with altered electrophysiological properties in organoids expressing the archaic variant. Our results suggest that the human-specific substitution in NOVA1, which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species’ evolution.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.