Monday, September 26, 2022

Neocortical Neurogenesis in Modern Humans Greater Than It Was in Neanderthals

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Neanderthal brains were similar in size to those of modern humans but differed in shape. What scientists cannot tell from fossils is how Neanderthal brains might have differed in function or organization of brain layers such as the neocortex, the outer region of the cerebral cortex. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics have now analyzed the effect of a single amino acid change in the transketolase-like 1 (TKTL1) protein on production of basal radial glia, the workhorses that generate much of the neocortex.

Pinson et al. suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals. Image credit: Neanderthal Museum.

The neocortex is an evolutionarily advanced brain structure responsible for cognitive abilities.

This structure is distinctly large and complex in humans, which is widely thought to endow our species with unique and extraordinary cognitive abilities.

However, the evolution of the neocortex in hominins isn’t well understood, and although fossil evidence indicates that the Neanderthal brains were similar in size to those of modern humans, how they might have differed in function or structure remains unknown.

Previous studies have shown that differences in neural progenitor cell populations can result in the variable size and shape of neocortices across living species.

In the new research, Dr. Anneline Pinson and her colleagues at the Max Planck Institute of Molecular Cell Biology and Genetics compared genomic sequences from modern humans with Neanderthals and other apes and discovered a unique amino acid substitution encoded in the TKTL1 gene of modern humans.

When placed in organoids or over-expressed in mouse and ferret brains, they found that the human TKTL1 variant (hTKTL1) drove more generation of basal radial glia neuroprogenitors than the archaic variant, which resulted in the proliferation of neocortical neurons.

Disrupting hTKTL1 expression or replacing hTKTL1 with the archaic variant in human fetal neocortical tissue and cerebral organoids resulted in reduced basal radial glia and neuron generation.

“We found that with the Neanderthal-type of amino acid in TKTL1, fewer basal radial glial cells were produced than with the modern human-type and, as a consequence, also fewer neurons,” Dr. Pinson said.

“This shows us that even though we do not know how many neurons the Neanderthal brain had, we can assume that modern humans have more neurons in the frontal lobe of the brain, where TKTL1 activity is highest, than Neanderthals.”

“Our study implies that the production of neurons in the neocortex during fetal development is greater in modern humans than it was in Neanderthals, in particular in the frontal lobe,” said Professor Wieland Huttner, senior author on the study.

“It is tempting to speculate that this promoted modern human cognitive abilities associated with the frontal lobe.”

The findings were published today in the journal Science.

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Anneline Pinson et al. 2022. Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science 377 (6611); doi: 10.1126/science.abl6422

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