Journal
SCIENCE
Volume 377, Issue 6611, Pages 1170-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abl6422
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Funding
- NOMIS Foundation
- ERA-NET NEURON (MicroKin)
- Max Planck Society
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This study found that the modern human variant hTKTL1, but not the Neanderthal variant, can increase the abundance of bRG without affecting bIPs, thereby affecting the generation of neocortical neurons. This indicates differences in neocortical neurogenesis between modern humans and Neanderthals.
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.
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