Summary:
Most primates, including humans, develop large, highly folded brains, but the common marmoset grows a notably smaller and nearly smooth neocortex. Using three-dimensional brain organoids together with fetal tissue, scientists at the German Primate Center (DPZ) have pinpointed cellular mechanisms that downscale cortical growth in marmosets. The team found that neural progenitor cells in marmosets divide more slowly, adopt simpler shapes with fewer processes, and experience a shorter period of rapid proliferation—changes that together reduce neuron production and limit cortical folding.
Key Facts:
- Cellular Braking Mechanisms: Marmoset neural progenitors progress through cell cycles more slowly and show simplified morphologies with fewer processes than human progenitors, which substantially reduces their overall neuron output.
- Truncated Proliferation Window: The developmental timeline in marmosets is compressed, giving progenitor populations a much shorter window for rapid expansion before they begin differentiating into neurons.
- Organoid-to-Tissue Staging: Comparative 3D organoid analysis showed that 50-day-old marmoset organoids correspond closely to 90-day fetal marmoset brain tissue, establishing organoids as a practical model to study primate brain evolution and developmental disorders affecting cortical folding.
Source: German Primate Center (DPZ) – Leibniz Institute for Primate Research
A hallmark of primate evolution is encephalization: the expansion of the cerebral cortex into a folded surface of sulci and gyri. Folding increases cortical surface area, accommodating billions of neurons and enabling more complex neural circuits. Evolutionary evidence suggests the common ancestor of living primates already had a moderately folded brain.
However, the common marmoset (Callithrix jacchus), a small New World monkey widely used in neuroscience research, is an exception: its neocortex remains largely smooth (lissencephalic) and compact. The recent study published in Science Advances by researchers at the DPZ identifies the developmental changes that drive this divergence from the folded primate cortex.
“We wanted to understand which cellular changes lead the marmoset brain to grow less and form fewer folds,” says Lidiia Tynianskaia, a doctoral researcher and co-first author. “Early in development, the marmoset cortex resembles that of a folded-brain primate, but later events must slow neuron production and alter growth dynamics to produce the smooth adult cortex.”
Neural Progenitors Hit the Brakes
To uncover how cortical folding is curtailed, the team generated comparative 3D brain organoids from both marmoset and human pluripotent stem cells and closely analyzed neural progenitor cells (NPCs)—the stem cell populations that generate the cerebral cortex’s neurons.
The experiments revealed convergent mechanisms that reduce neurogenesis in marmosets:
- Slower Division Rates: Specific progenitor subtypes in marmosets progress through fewer divisions per unit time than their human counterparts, producing fewer daughter cells and lowering overall neuronal output.
- Simplified Cell Architecture: Some marmoset progenitors develop simpler morphologies with fewer processes and contact points, which correlates with reduced capacity to proliferate and generate additional progenitors.
- Shortened Proliferative Timing: The period during which progenitors expand rapidly is temporally truncated in marmosets, effectively closing the window that would otherwise support large-scale neuron production and extensive cortical folding.
“Certain progenitor populations in the common marmoset divide considerably more slowly and present less complex shapes than their human equivalents,” explains co-first author César Mateo Bastidas Betancourt. “Together, these adaptations lower neuron numbers and contribute to a smaller, smoother cortex in marmosets.”
Organoid Models Align with Fetal Neurodevelopment
Three-dimensional organoid cultures allowed the researchers to model primate neurodevelopment with sufficient sample sizes for robust statistical analysis while preserving key physiological features. The organoid platform enabled parallel study of marmoset and human developmental trajectories under controlled conditions.
“Combining in vitro organoids with targeted validation in fetal tissue marries the strengths of both approaches,” says Michael Heide, Ph.D., leader of the Junior Research Group Brain Development and Evolution. “Organoids provide the statistical power that primate studies alone cannot, and our fetal tissue comparisons confirm that organoid observations reflect in vivo development.”
By benchmarking developmental stages across organoids and fetal tissue, the team determined that 50-day-old marmoset organoids closely match the cellular composition and maturation state of 90-day fetal marmoset neocortex. This temporal calibration made it possible to align key milestones and demonstrate how modest shifts in progenitor behavior can reshape cortical architecture.
Understanding how progenitor dynamics control cortical size and folding also has clinical relevance. The cellular programs uncovered in marmosets illuminate mechanisms that, when disrupted in humans, can lead to congenital conditions such as lissencephaly or microcephaly—disorders in which cortical folding and neuron number are severely affected.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was provided by editorial staff.
About this Depression Research:
- Media Contact: Susanne Diederich
- Source: DPZ
- Image Credit: Image credited to Lidiia Tynianskaia – German Primate Center
- Original Research is Open Access: Science Advances (August 31, 2026). “Coordinated neural progenitor adaptations contribute to primate neocortical downscaling.” Authors: Lidiia Tynianskaia, César Mateo Bastidas-Betancourt, Esther Marie Grewe, Julia Marie Kniep, Neringa Liutikaite, Nesil Esiyok, İrfan Burak Göloğlu, Sabrina Heide, Nancy Rüger, Dimitri Lindenwald, Charis Drummer, Stoyan Petkov, Nataliya Di Donato, and Michael Heide.
- DOI: 10.1126/sciadv.aeg5563
Abstract
Coordinated neural progenitor adaptations contribute to primate neocortical downscaling
Most primates develop a large, highly folded (gyrencephalic) neocortex—a trait thought to have been present in the primate common ancestor. In contrast, several New World monkey species, including the common marmoset, retain a comparatively small and largely smooth (lissencephalic) neocortex. This phenotype likely reflects evolutionary reduction from the ancestral condition and implies modifications to neurodevelopmental programs.
One central driver of neocortical development is the behavior of neural progenitor cells. By combining marmoset and human cerebral organoids with analyses of fetal marmoset neocortical tissue and previously published histological data, the study uncovers multiple adaptations in apical and basal progenitors. These coordinated changes converge on reduced progenitor capacity, altered early progenitor dynamics, and constrained neuronal output, thereby limiting the size and folding of the marmoset neocortex.