Researchers at the Center for Regenerative Therapies Dresden and TUD Dresden University of Technology have identified nearly 600 regulatory DNA sequences that are more active in human neural stem cells than in comparable chimpanzee and gorilla cells. The findings offer an explanation for how the human neocortex produces a larger population of neurons despite the close similarity between the coding genomes of great apes.
The team cultivated three-dimensional cerebral organoids from induced pluripotent stem cells obtained from humans, chimpanzees and gorillas. These models allowed the researchers to examine early neural development, a stage that cannot be directly studied using protected great ape embryonic brain tissue.
The study focused on basal radial glia, neural progenitor cells that contribute to neocortex development. Instead of finding many uniquely human protein-coding genes, the researchers observed differences in the activity of shared genes. The identified DNA sequences act as enhancers, regulating how strongly genes are expressed in human neural stem cells.
Many of the affected genes are involved in the cytoskeleton and cell structure. Their increased activity promotes long, branched extensions in neural stem cells. These extensions may allow progenitor cells to receive more signals from their surrounding cellular environment, helping them remain capable of dividing and delaying premature differentiation.
The researchers tested this mechanism by reducing the activity of two switch-regulated genes, FAM107A and CNGA3, in human cerebral organoids. The neural stem cells became less branched and showed reduced proliferation, ultimately producing fewer neurons. The results link the cells’ morphology with their ability to sustain neurogenesis.
The study supports the idea that human brain evolution involved changes in gene regulation rather than the wholesale invention of new genes. In this view, humans and other great apes largely use the same biological machinery, but regulatory elements adjust that machinery differently during development.
The research was published in Nature Communications under the title “Human-specific morphoregulatory signatures in basal radial glia characterise neocortex evolution.”
Sources: Neuroscience News.