We humans have an exceptionally large brain in relation to our height. This is the basis for our higher cognitive skills. But which genes are responsible for our extraordinary brain growth? A new study now shows, like two genes that only occur in humans, during embryonic development and ensure that neuronal predecessor cells multiply. The findings provide new insights into the development of the unique human brain.
Over the past two million years, the human brain has gained significantly in size. Above all, the neocortex, part of the cerebrum, which is the seat of our higher cognitive functions, is three times larger than our closest relatives, the chimpanzee. Earlier studies had already shown that some genes only occurred in humans ensure extraordinary growth and the strong folding of the human cerebral cortex. Accordingly, genes of the so-called Notch2NL family are involved. Notch genes are widespread in the animal kingdom and control the growth of different organs. The uniquely human variants help our brain to make its size. How exactly they boost growth was still unclear.
Two genes in the function test
A team around Nesil Eşiyok from the German Primate Center in Göttingen has now examined, as a member of this gene family, called notch2NLB, plays together with another neighboring gene called NBPF14. In order to find out the function of these genes, the researchers injected the MRNA blueprints for the corresponding gene products in the brain cells of mouse embryos. After 24 and 48 hours, they observed how the human proteins produced on the basis of these genetic building instructions had an effect on the development of the embryonic brain.
In harmony with previous studies, Eşiyok and her team found that notch2nLB ensures that the precursor cells of the brain cells multiply and share new forerunner cells. Mouse embryos that had received the blueprint for Notch2NLB had a larger pool of these cells available. However, more progenitor cells alone are not sufficient so that a larger brain is actually created. It is also important that the forerunners develop in order to finally form nerve cells.
Propagation and further development
This is where the gene NBPF14 comes into play, the function of which was still largely unknown. As the researchers found out, NBPF14 ensures that the precursor cells convert into another, more advanced type of progenitor cells that later become neurons. “When NBPF14 and NOTCH2NLB are expressed together, they have coordinated effects that lead to the first level of progenitor cells to develop to the next stage, while a large pool of the original preliminary cells is preserved and renewed themselves,” reports the team.
The same distribution of tasks of the two genes showed up when the researchers also checked their results to so -called brain organoids, which they had bred from stem cells from chimpanzees. “The special thing about our study is that the results of animal experiments and alternative methods ideally complement each other and confirm each other,” says Eşiyok’s colleague Michael Heide. “This not only underlines the high meaning of our results, but could also help reduce the need for animal experiments in the future by further developing, refining and confirming alternative methods.”
Source: Nesil Eşiyok (Deutsches Primatenzentrum GmbH, Leibniz Institute for Primate Research, Göttingen) et al., Science Advances, Doi: 10.1126/sciadv.ads7543