Stem‑Cell Brain Organoids Reveal Why Most Primates Have Folded Brains While Marmosets Do Not

Scientists using stem‑cell derived brain organoids have identified developmental mechanisms that explain why the majority of primate species develop highly folded cerebral cortices, whereas the small common marmoset (Callithrix jacchus) retains a smooth, almost completely unfolded brain surface.

The study, reported on Phys.org, compared organoids generated from marmoset cells with those from species that display pronounced gyri and sulci. By tracking the growth of neural tissue in a controlled laboratory setting, researchers observed distinct patterns of cell proliferation and migration that correspond to the emergence of cortical folds in the latter group.

In primates with larger brains, the rapid expansion of the cortical plate creates mechanical forces that buckle the tissue, producing the characteristic ridges and valleys that increase surface area. The organoid experiments showed that this expansion is driven by a burst of neuronal progenitor activity early in development, a process that is markedly muted in marmoset‑derived organoids.

Conversely, the marmoset organoids exhibited a more uniform growth trajectory, lacking the localized over‑growth that triggers folding. This suggests that the evolutionary reduction in cortical progenitor proliferation may be a key factor behind the species’ smooth brain morphology, which in turn influences neural connectivity and possibly behavioral repertoires.

Understanding the cellular basis of brain folding has broader implications for both evolutionary biology and medicine. The degree of cortical gyrification varies widely across mammals and is linked to cognitive capacity; abnormalities in folding are also hallmarks of several neurodevelopmental disorders. By isolating the specific developmental programs that generate folds, the research offers a platform for testing how genetic or environmental disruptions might lead to malformations.

Future work will likely extend the organoid model to additional primate lineages, enabling a comparative map of folding mechanisms across the evolutionary tree. Such efforts could illuminate how subtle changes in early brain development have contributed to the diverse cognitive abilities observed among primates, and may eventually inform therapeutic strategies for human brain disorders linked to abnormal cortical architecture.