Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals.

Bibliographic Collection: 
APE, CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Pinson, Anneline; Xing, Lei; Namba, Takashi; Kalebic, Nereo; Peters, Jula; Oegema, Christina Eugster; Traikov, Sofia; Reppe, Katrin; Riesenberg, Stephan; Maricic, Tomislav; Derihaci, Razvan; Wimberger, Pauline; Pääbo, Svante; Huttner, Wieland B
Year of Publication: 2022
Journal: Science
Volume: 377
Issue: 6611
Pagination: eabl6422
Date Published: 2022 Sep 09
Publication Language: eng
ISSN: 1095-9203
Keywords: Animals, Ependymoglial Cells, Ferrets, Humans, Mice, Neanderthals, Neocortex, Neurogenesis, Transketolase

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.

DOI: 10.1126/science.abl6422
Alternate Journal: Science