A gene that is responsible for brain size in modern Homo sapiens and their ancient relatives, Neanderthals and Denisovans, has been identified by a team of scientists from Germany led by Dr Wieland Huttner of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden.

In their study, Dr Huttner and his colleagues from the Technical University of Dresden and the Max Planck Institute for Evolutionary Anthropology isolated different subpopulations of human brain stem cells and precisely identified which genes are active in which cell type.

In doing so, they noticed that one particular gene contributed to the reproduction of basal brain stem cells, triggering a folding of the neocortex.

The scientists said: “this gene manages to trigger brain stem cells to form a bigger pool of stem cells. In that way, during brain development more neurons can arise and the cerebrum can expand. The cerebrum is responsible for cognitive functions like speaking and thinking.”

According to the team, the gene, called ARHGAP11B, is found in modern-day humans and our ancient relatives, Neanderthals and Denisovans, but not in chimpanzees.

Dr Huttner and his colleagues developed a method that isolates and identifies special subpopulations of brain stem cells from the developing human cerebrum; no one has managed to do this so far.

First, they isolated different stem and progenitor cell types from fetal mice and human cerebrum tissue.

They then compared the genes that are active in the various cell types and were able to identify 56 genes that play a role in brain development.

“We noticed that ARHGAP11B is especially active in basal brain stem cells. These cells are really important for the expansion of the neocortex during evolution,” said Marta Florio, a PhD student at the Max Planck Institute of Molecular Cell Biology and Genetics and the first author of the paper published in the journal Science.

The researchers then focused on the function of ARHGAP11B. They suspected that if it was responsible for a bigger pool of brain stem cells in humans and thereby for an expanded cerebrum, then it should trigger a similar development in the smaller brain of a mouse.

They introduced it into mice embryos and under its influence the mice produced significantly more brain stem cells and in half of all cases even a folding of the neocortex, which is typical for human brains.

“All these results suggest that the gene ARHGAP11B plays a key role in the evolutionary expansion of the human neocortex,” the scientists said.

“ARHGAP11B is the first human-specific gene where we could show that it contributes to the pool of basal brain stem cells and can trigger a folding of the neocortex. In that way, we managed to take the next step in tracing evolution,” Dr Huttner said.

_____

Marta Florio et al. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science, published online February 26, 2015; doi: 10.1126/science.aaa1975