Grow big
Biologists have found the genes that make our brains grow big
Sergey Vasiliev, Naked Science
Everyone knows that the human brain is one of the largest on the planet and exceptionally large for the size of our body. However, until now, no one could say exactly how it reaches its impressive size. This is explained by two recent papers, the results of which are presented in articles published in the journal Cell (1, 2). The teams of Pierre Vanderhaeghen from the Free University of Brussels and David Haussler from the University of California, Santa Cruz describe the NOTCH2NL gene family involved in the growth of brain volume.
"Given the rather rapid evolution of the human brain," says Pierre Vanderhagen, "it is tempting to assume that it is the new, human–specific genes that are responsible for this process." Indeed, the NOTCH2NL genes are unique to our species: they are not found in either macaques or orangutans, and even in species as close to us as gorillas and chimpanzees, although they are present, they remain inactive. In humans, NOTCH2NL work, apparently, prolonging the life of stem cells-precursors of neurons, so that they have time to produce more divisions and give life to more cells of the emerging brain.
Pierre Vanderhagen and his colleagues analyzed RNAs that are synthesized from active genes during corticogenesis in human embryos. This allowed us to identify a group of 35 young, specific genes for us. The whole family turned out to be paralogs (modified copies) of the Notch 2 receptor gene, already familiar to scientists and very ancient. It is known that it is involved in the development of the body in fruit flies and stimulates the production of neurons in the brain.
Indeed, experiments on mice and human pluripotent stem cells have shown that the result of the action of the NOTCH2NL genes is an increase in the number of new neurons. "From one stem cell, you can get either two progenitor cells that will give two neurons, or one progenitor and one neuron," explains Pierre Vanderhagen. "And NOTCH2NL shifts the choice between these options towards two progenitor cells, which eventually leads to the appearance of more neurons."
Scientists from David Hossler's group came to similar results, who began by comparing the activity of genes in the emerging brain of a macaque and a human. One of the main differences turned out to be the NOTCH2NL family. The researchers removed these genes from stem cells and started their development towards the nervous tissue, showing that mature neurons appear faster, but the pool of stem cells is exhausted earlier, managing to produce noticeably fewer neurons.
A careful analysis of the DNA sequence of the NOTCH2NL genes allowed scientists to find a small section 1q21.1, changes in which are associated with some disorders of brain development. Apparently, the activity of NOTCH2NL led not only to an increase in brain volume in our ancestors, but also made us susceptible to the development of conditions such as micro- and macrocephaly.
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