[en] 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.
Disciplines :
Neurology
Author, co-author :
Pinson, Anneline ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Xing, Lei ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Namba, Takashi; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Kalebic, Nereo ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Peters, Jula ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Oegema, Christina Eugster ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Traikov, Sofia; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Reppe, Katrin; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Riesenberg, Stephan ; Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
Maricic, Tomislav ; Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
Derihaci, Razvan ; Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, 01307 Dresden, Germany
Wimberger, Pauline ; Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, 01307 Dresden, Germany
Pääbo, Svante ; Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
Huttner, Wieland B ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
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