2023/08/08 by Lei Xing, Anneline Pinson, Felipe Mora‐Bermúdez +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Mitochondrial Function and Pathology #Neurogenesis and neuroplasticity mechanisms #RNA Research and Splicing
paper · doi:10.1002/9781119860914.ch8
openalex publication_date 2023/08/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/02
The neural stem and progenitor cells (NSPCs) in the developing neocortex have a key role in its expansion and in neocortical neurogenesis. Here, we summarize the key features of the two principal classes of neocortical NSPCs, the apical progenitors (APs) residing in the ventricular zone (VZ) and the basal progenitors (BPs) residing in the subventricular zone (SVZ). We explain how the differences in the cell biology of BPs vs. APs endow the former class of NSPCs with a crucial advantage for neocortex expansion in development and evolution. Next, we discuss the human-specific gene ARHGAP11B and its ability to amplify BPs, which is based on the localization of the ARHGAP11B protein in mitochondria and its stimulation of the metabolic pathway glutaminolysis, eventually resulting in increased neocortical neurogenesis and neocortex expansion. Finally, we address the crucial roles of modern human-specific amino acid substitutions in proteins that govern fundamental aspects of neocortical development. Thus, three such substitutions in KIF18a and KNL1 reduce the rate of chromosome segregation errors upon AP mitosis, implying less of these errors in the radial units of modern human than Neanderthal neocortex. Furthermore, a single modern human-specific amino acid substitution in transketolase-like 1 (TKTL1) underlies its ability to selectively amplify basal radial glia, the BP type generating most neocortical neurons. As a result, TKTL1 is implicated in greater neocortical neurogenesis in modern humans than Neanderthals, notably in the frontal lobe.