2022/09/08 by Anneline Pinson, Lei Xing, Takashi Namba +11 · 1 citation
Biochemistry, Genetics and Molecular Biology · #RNA modifications and cancer #RNA Research and Splicing #Nuclear Structure and Function
paper · doi:10.1126/science.abl6422
openalex publication_date 2022/09/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals.