Lab-Grown Mini-Brains Hint At What Separates Humans From Apes

Humans and Apes Share Genes but Use Them Differently

Humans and apes run on nearly the same genes, yet the human brain grew far larger. A study in Nature Communications points to how those genes are used rather than which ones are present. Nearly 600 DNA switches that control genes were more active in a type of human neural stem cell than in chimpanzee or gorilla versions of that cell. Two of the genes involved, one best known for its role in the eye, help shape the cells that churn out the brain’s neurons.

Humans have a far larger neocortex, the brain’s outer layer for abstract thinking, long-term planning, and speech, than other great apes do. Some genes found only in humans have been linked to bigger brains, but they do not account for all of that growth. Meanwhile, the part of the human genome that makes proteins is 98 to 99 percent identical to that of chimpanzees and gorillas. Studying how the gap arises has been hard, because developing brain tissue from great apes is off-limits to researchers, and the animals are endangered and protected.

Prof. Mareike Albert, who led the study at TUD Dresden University of Technology, said humans use “largely the same toolkit as apes, just with different settings.” Organoids, tiny brain-like tissues grown from stem cells, “give us a window into a stage of development that we otherwise could not study at all,” she added.

Nearly 600 DNA Switches Are More Active in Human Brain Cells

Researchers made the mini-brains from one chimpanzee cell line, one gorilla line, and three human lines, and let each grow about eight weeks, a stage when the key cell types are present and when brain development appears to line up across the three species. Results were checked against donated human fetal brain tissue from weeks 13 to 14 of pregnancy.

Next, the researchers looked at which DNA switches were turned on in a type of neural stem cell called basal radial glia. Dr. Theresa Schütze, who led the experimental work, described the switches as “dimmers that turn genes up or down.” In human cells, 599 of them were more active than in chimpanzee or gorilla cells, and the pattern held up in the fetal tissue.

Many of the genes those switches help control shape mature neurons, including their projections, the long extensions that reach out and connect to other cells. Human stem cells ran those shape-building genes at a level that nearly matched mature neurons and topped chimpanzee stem cells. In other words, these cells seem to borrow tricks usually reserved for fully grown neurons. Activity alone does not show actual shapes, though, so the team put two genes to the test.

Switching Off Either Gene Reduces Elaborate Shapes in Human Brain Cells

From the many genes flagged, the team picked FAM107A, tied to human stem cells in earlier work, and CNGA3, known mainly for its role in cone cells, the eye’s light sensors. Both ran far more actively in human cells than in ape cells, and CNGA3 was nearly absent in chimpanzee cells.

Gene editing then switched off each gene separately in human mini-brains, across three independent batches. Either way, fewer cells developed elaborate shapes. Earlier research suggests stem cells with more reach pick up more signals from their surroundings, much as a plant with more leaves catches more sunlight, and go on to make more neurons. Closer measurements showed that only the FAM107A edit cut the number of projections growing straight from the cell body, and it also led to fewer neurons in the tissue. Shutting down CNGA3 changed none of the individual measurements, so its exact role is less certain.

Lab tests of the DNA switches near each gene added a clue. In mouse cells, the human switch near FAM107A boosted gene activity while the chimpanzee version did not clearly do so, and the human switch near CNGA3 outperformed its chimpanzee counterpart. Adding extra human FAM107A to chimpanzee mini-brains did not make cells more elaborate. It had an effect similar to switching the gene off in human tissue, hinting that the amount of this gene may need to land in a narrow range.

Different Gene Settings May Help Explain Human Brain Evolution

Human brain growth likely involved a few big-effect genes plus many small genetic changes, and the authors note that small effects are hard to catch in experiments. The team also flagged several other genes tied to cell growth that may work alongside these two, so the full story likely involves a crowd, not a pair. Silencing the switch near FAM107A lowered the gene’s activity only slightly, and the authors suggest backup switches may step in. Whether chimpanzee cells would change shape if given the human versions of these switches was not tested here.

Two genes cannot account for human intelligence, and mini-brain experiments cannot prove these changes enlarged the human neocortex. Even so, the work backs one idea: what sets humans apart may come partly from how shared genes are set, not only from genes that are new.

---

Disclaimer: This article summarizes a scientific study for general information only and is not medical advice. Findings from lab-grown mini-brains may not match real brain development in people or apes, and more research is needed before firm conclusions can be drawn.

---