A microscopy picture of a human brain organoid. The organoid was stained with a special dye to highlight cell shape and branches.
Image Credit: © Theresa Schütze, Albert Group, CRTD
Scientific Frontline: Extended "At a Glance" Summary: Human Neocortex Evolution
The Core Concept: The evolutionary expansion of the human neocortex is driven not only by novel genetic sequences but by the unique upregulation of shared genes via specific non-coding genetic switches that alter neural stem cell morphology.
Key Distinction/Mechanism: Although Homo sapiens share 98 to 99 percent of their coding genome with chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla), researchers identified nearly 600 genetic switches that are significantly more active in human neural stem cells. These switches function as "dimmers," increasing the cellular branching of stem cells, which allows them to process more environmental signals, divide more frequently, and ultimately generate a larger volume of neurons.
Origin/History: Published in October 2026 by an international team led by researchers at the Technical University of Dresden, this discovery was made possible by utilizing laboratory-grown brain organoids to bypass the ethical barriers of researching fetal ape brain tissue.
Major Frameworks/Components:
- Brain Organoids: Three-dimensional, in vitro tissue cultures grown from stem cells utilized to accurately model the early developmental stages of the neocortex in humans and great apes.
- Genetic Switches: Short, non-coding sequences of DNA (enhancers) that regulate the expression levels of target genes without altering the fundamental genetic code.
- Basal Radial Glia: A specialized population of neural stem cells responsible for neuron production, which in humans display heightened structural branching that directly correlates to increased neurogenic capacity.
Branch of Science: Evolutionary Biology, Neuroscience, Genetics
Future Application: Utilizing stem cell-derived organoids to map species-specific genetic pathways establishes a vital framework for investigating early neurodevelopment, which could inform future therapeutic approaches for neurodevelopmental and neurodegenerative disorders.
Why It Matters: This research resolves a critical question regarding human cognitive evolution—specifically the exponential growth of the neocortex, which governs abstract thought, long-term planning, and language—by demonstrating that how species regulate and utilize their genes is just as crucial as the genome itself.
How did the human brain become so much larger than that of our closest evolutionary relatives? Part of the answer lies not in new genes, but in how humans and nonhuman apes use the genes they share. Using lab-grown brain organoids, an international team led by Professor Mareike Albert at TUD Dresden University of Technology compared early brain development in humans, chimpanzees, and gorillas. They found that in humans, genetic switches make certain genes more active, which likely causes the cells that build the brain to become more branched—a trait linked to producing more neurons and, in turn, a bigger brain. The study is published in the journal Nature Communications.
In the brain, the neocortex is the area responsible for higher cognitive functions such as abstract thinking, long-term planning, and speech. The human neocortex is much larger than that of other great apes. Although certain human-specific genes have been linked to a larger brain, they alone do not explain the massive evolutionary expansion of the human neocortex.
“Changes in brain size actually arise during development. This is when the majority of neurons are generated. But developing brain tissue of nonhuman great apes is not available for research, and for good ethical reasons,” explains Professor Mareike Albert, research group leader at the Center for Regenerative Therapies Dresden (CRTD) and the Faculty of Biology of TUD Dresden University of Technology, who led the study. “So we asked: How can we still compare brain development of different species side by side?”
The answer was brain organoids: tiny, three-dimensional tissue structures grown from stem cells. Organoids resemble the developing brain, in this case, the neocortex. The researchers grew organoids from human, chimpanzee, and gorilla stem cells and compared the early stages of brain development between the species. They found clear differences in how the three species use their shared genes.
Same Genes, Different Settings
The human coding genome is 98% to 99% identical to that of chimpanzees and gorillas. Yet identical genes are not necessarily used in the same way. The team analyzed the gene activity in the neural stem cells in developing brain organoids and found that many genetic switches operate differently in humans.
“These genetic switches are short DNA sequences that control how active a gene is. You can think of them as sort of dimmers that turn genes up or down,” says Dr. Schütze, who led the experimental part of the study. “We found nearly 600 switches that are more active in human neural stem cells than in those of chimpanzees and gorillas.”
Many of these switches regulated genes known to shape the cell, especially helping a cell grow long, branched extensions. When the researchers switched off two of these genes in human organoids, the stem cells became less branched, and, in one case, the cells gave rise to fewer neurons. This is in line with earlier research suggesting that more branched stem cells pick up more signals from their surroundings, divide more often, and produce more neurons, which, in turn, leads to a bigger brain.
“It is not necessarily different genes that make a human brain special. As the nearly identical genomes suggest, we use largely the same toolkit as apes, just with different settings,” says Professor Albert.
A New Window into Early Development
Great apes are endangered and strictly protected. As a result, how the brain of our closest living relatives develops has remained largely out of reach for research.
“Organoids give us a window into a stage of development that we otherwise could not study at all,” says Professor Albert. “What makes us human is a fascinating question. With organoids, we can finally start answering parts of this question at the level of individual cells and genes.”
Reference material: What Is: Organoid
About the Study: The study is the result of an international collaboration with partners in Dresden (MPI-CBG, University Hospital Carl Gustav Carus, NCT/UCC Dresden), Munich (Helmholtz Munich), Hannover (Hannover Medical School), Milan (Human Technopole), Cambridge (MRC Laboratory of Molecular Biology), London (King’s College London), and Helsinki (University of Helsinki).
Published in journal: Nature Communications
Title: Human-specific morphoregulatory signatures in basal radial glia characterise neocortex evolution
Authors: Theresa M. Schütze, Annika Kolodziejczyk, Nora Ditzer, Silvia Vangelisti, Emanuele Capra, Jeong-Eun Lee, Ilaria Chiaradia, Vida Kufrin, Seiya Yamada, Jula Peters, Maximilian Krause, Christina Eugster Oegema, Razvan P. Derihaci, Cahit Birdir, Takashi Namba, Alexander A. Wurm, Ulrich Martin, Pauline Wimberger, Katherine R. Long, Madeline A. Lancaster, Nereo Kalebic, Boyan Bonev, and Mareike Albert
Source/Credit: Technische Universität Dresden
Edited by: Scientific Frontline
Reference Number: ebio102726_01
