A number of evolutionary mechanisms are proposed to have contributed to the rapid increase in cortical size and complexity in the human lineage. These include gene duplication events and the resulting emergence of novel human-specific gene paralogues. Two recent papers now provide evidence that the appearance of human-specific paralogues of NOTCH2 had a role in human cortical expansion. The findings of Fiddes et al. and Suzuki et al. together reveal that members of a group of human-specific NOTCH2 N-terminal-like (NOTCH2NL) genes are expressed in human cortical progenitors, including the radial glial cells that are thought to have a crucial role in cortical expansion, and demonstrate that NOTCH2NL proteins can activate Notch signalling pathways. They show that expression of NOTCH2NL genes in human and mouse cortical progenitors delays their exit from the cell cycle, prolonging neurogenesis, and may thereby have contributed to the growth in brain size in humans.
Fiddes, I. T. et al. Human-specific NOTCH2NL genes affect Notch signalling and cortical neurogenesis. Cell 173, 1356–1369 (2018)
Suzuki, I. J. et al. Human-specific NOTCH2NL genes expand cortical neurogenesis through Delta/Notch regulation. Cell 173, 1370–1384 (2018)
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Whalley, K. Expanding knowledge. Nat Rev Neurosci 19, 444 (2018). https://doi.org/10.1038/s41583-018-0034-z