Human, chimpanzee and gorilla brain organoids revealed differences in how developing stem cells regulate shared genes.Researchers identified 599 candidate regulatory regions with greater accessibility in human basal radial glia and tested two cell-shape genes.The findings connect gene regulation with stem-cell structure, but do not establish a complete explanation for human brain expansion.<\/p>\n
The cells that build the human brain may owe part of their distinctive behavior to different settings on familiar genes. Comparing laboratory-grown tissues from humans, chimpanzees and gorillas, researchers found regulatory differences linked to the shape of neural stem cells. Disrupting two genes changed those cells\u2019 structural complexity, and one disruption also reduced neuron numbers.<\/p>\n
The international study, led by Mareike Albert at TUD Dresden University of Technology<\/a>, appeared in Nature Communications<\/a>. It investigates how changes in gene regulation<\/a> could contribute to the evolutionary expansion of the neocortex. This brain region supports abilities including speech, abstract thinking and long-term planning, but the experiments did not measure those abilities.<\/p>\n Comparing development without studying living ape brains<\/p>\n Differences in adult brain size begin much earlier, while developing stem cells are producing neurons. Human-specific genes explain some relevant developmental mechanisms, but they do not account for the full expansion of the human neocortex. Researchers therefore need ways to compare how shared genetic instructions operate during development.<\/p>\n A microscopy picture of a human brain organoid. The organoid was stained with a special dye to highlight cell shape and branches. (CREDIT: Theresa Sch\u00fctze \/ CRTD) <\/p>\n \u201cChanges in brain size actually arise during development. This is when the majority of neurons are generated. But developing brain tissue of non-human great apes is not available for research, and for good ethical reasons,\u201d said Albert, who leads a group at Dresden\u2019s Center for Regenerative Therapies. Her team turned to organoids as an alternative route into that otherwise inaccessible period.<\/p>\n Brain organoids<\/a> are three-dimensional tissue models grown from stem cells that reproduce selected features of a developing brain. Here, the researchers generated models from all three species and compared early neocortical development. These models allow controlled cellular experiments, while remaining different from complete brains developing inside living animals.<\/p>\n A 2021 comparative organoid study<\/a> examined an earlier transition in the shape of developing human and ape cells. Delaying that transition in human organoids was associated with larger models. Together, such experiments show why researchers examine multiple developmental stages rather than seeking one universal explanation for brain expansion.<\/p>\n Shared genes can have different settings<\/p>\n Having similar protein-coding genes does not mean two species use them with identical timing or intensity. Regulatory DNA helps determine where, when and how strongly genes operate. A change in that control system can affect development without requiring an entirely new protein-coding gene.<\/p>\n \u201cThese 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,\u201d said Theresa M. Sch\u00fctze, who led the experimental work. The dimmer analogy emphasizes differences in activity levels, rather than a simple division between genes being present or absent.<\/p>\n Cell type-specific ATAC-seq reveals distinct cellular profiles in great ape corticogenesis. (CREDIT: Mareike Albert et al, Nature Communications 2026) <\/p>\n The team identified 599 candidate regulatory regions with greater DNA accessibility in human basal radial glia than in the corresponding ape cells. Basal radial glia are neural progenitors involved in building the neocortex. Accessibility helps identify potentially active regulatory regions, but the full list should not be read as 599 individually proven causes of brain enlargement.<\/p>\n Why the shape of a stem cell matters<\/p>\n Many of the highlighted regions were associated with genes involved in shaping cells and their extensions. That pattern directed attention toward how elaborate a progenitor cell\u2019s structure becomes. The researchers were interested in the cells producing neurons, rather than simply comparing the final shapes of mature nerve cells.<\/p>\n Earlier work has connected more complex progenitor shapes with greater capacity to generate neurons. In a 2019 study<\/a>, researchers linked the number of cellular extensions with progenitor proliferation across experimental systems. This background gives the Dresden findings a plausible developmental context, rather than proving that every additional extension necessarily produces a larger brain.<\/p>\n That earlier work examined a protein called PALMDELPHIN and found that increasing its expression promoted progenitor extensions and proliferation in mouse and ferret tissue. Disrupting its gene in human fetal tissue reduced both. The findings helped establish cell shape as a functional part of developmental biology, rather than merely a visible difference between species.<\/p>\n One proposed explanation is that more elaborate cells encounter more growth-promoting signals in their surroundings. Their extensions could increase contact with the local environment and provide access to signals from different sources. Under that model, cellular signaling<\/a> connects physical structure with decisions about division and neuron production.<\/p>\n Human-specific patterns of chromatin accessibility in bRG link to cell morphology genes. (CREDIT: Mareike Albert et al, Nature Communications 2026) Testing two genes moved beyond comparison<\/p>\n