Summary:
While most primates, including humans, possess large and highly folded brains, common marmosets develop smaller brains with smooth, virtually unfolded surfaces. Using brain organoids and fetal tissue, researchers at the German Primate Center discovered that this difference stems from distinct cellular braking mechanisms in neural progenitor cells, which divide more slowly, adopt simpler branching structures, and exhibit a shortened developmental window for rapid proliferation.
Key Facts:
- Cellular Braking Mechanisms: Marmoset neural progenitor cells divide significantly slower and display simpler morphologies with fewer cellular processes than human progenitors, substantially curbing total neuron generation.
- Truncated Proliferation Window: The developmental timeline in marmosets is temporally compressed, offering progenitor cells a much shorter period to rapidly multiply before differentiation begins.
- Organoid-to-Tissue Staging: Comparative analysis of 3D brain organoids revealed that 50-day-old marmoset organoids mirror natural 90-day fetal brain tissue, providing a reliable platform to study primate evolutionary brain divergence and neurodevelopmental disorders.
Source: German Primate Center (DPZ) – Leibniz Institute for Primate Research
A hallmark of primate evolution is encephalization: the emergence of an expanded cerebral cortex characterized by deep furrows (sulci) and raised ridges (gyri). This cortical folding dramatically amplifies surface area, providing room for billions of densely interconnected neurons capable of supporting complex cognition. Evolutionary biologists believe that even the common ancestor of all living primates possessed a moderately sized, folded brain.
Yet, the common marmoset (Callithrix jacchus), a small New World monkey native to South America and widely studied in biomedical research, stands as a striking exception. Its brain remains almost completely smooth (lissencephalic) and compact.
Now, a study published in Science Advances by neuroscientists at the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen identifies the developmental pivot points responsible for this divergence.
“We wanted to understand which changes at the cellular level cause the marmoset brain to grow less and form fewer folds,” explains co-first author Lidiia Tynianskaia, a doctoral researcher in the Junior Research Group Brain Development and Evolution at the DPZ. “At the beginning of development, the common marmoset brain exhibits the typical structure and composition of a large, folded primate brain. As development progresses, processes must therefore occur that effectively slow down the production of nerve cells.”
Neural Progenitors Hit the Brakes
To trace how cortical folding is curtailed, the researchers generated comparative 3D brain organoids derived from both common marmoset and human stem cells, focusing on the behavior of neural progenitor cells—the stem cells responsible for generating the entire cortical neuronal population.
The experiments revealed a coordinated, multi-tiered downregulation of neurogenesis in marmosets:
- Slower Division Rates: Progenitor subpopulations in marmosets divide significantly slower than their human counterparts, yielding fewer daughter cells per cell cycle.
- Simplified Cell Architecture: Certain marmoset progenitor cells develop simpler physical structures with fewer processes and contact points, directly reducing their proliferative potential.
- Shortened Proliferative Timing: Marmoset progenitors undergo a temporal shift that curtails their high-proliferation phase, shutting down the developmental window required to build a heavily folded cortex.
“Our investigations have shown that certain progenitor cells in the common marmoset divide significantly more slowly than in humans,” notes co-first author César Mateo Bastidas Betancourt. “Other progenitor cells have a simpler structure than their human counterparts, with fewer processes, and are therefore less proliferative. Both of these factors ultimately result in fewer nerve cells, which contributes to a smaller size and less folding of the cerebral cortex in marmosets.”
Organoid Models Align with Fetal Neurodevelopment
Recreating primate neurodevelopment in three-dimensional organoid cultures allowed the team to overcome sample size limitations while maintaining physiological relevance.
“The study combines the advantages of in vivo and in vitro methods,” says Michael Heide, Ph.D., leader of the Junior Research Group Brain Development and Evolution. “Organoids are well-suited for obtaining statistically robust results because such sample sizes are not feasible in primates. We subsequently repeated some key experiments in fetal brain tissue to confirm the results from the organoids.”
By bench-marking development across systems, the team determined that 50-day-old marmoset brain organoids correspond closely to natural embryonic brain tissue at day 90 of gestation. This temporal calibration enabled the researchers to align developmental milestones precisely and demonstrate how subtle shifts in progenitor dynamics alter cortical architecture.
Beyond charting primate evolution, deciphering the cellular controls of cortical folding provides an essential foundation for understanding human congenital malformations, such as lissencephaly and microcephaly, where normal folding programs fail to initiate.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our 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, Cesar 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 have a large, highly folded (gyrencephalic) neocortex, a feature present in the primate common ancestor. In contrast, several New World monkey species display a comparatively small and largely smooth, unfolded (lissencephalic) neocortex.
One prominent example is the common marmoset, an increasingly popular model in neuroscience. This phenotype likely reflects an evolutionary reduction from the ancestral primate condition, implying modifications in neurodevelopmental programs. One essential basis for neocortical development is the activity and behavior of neural progenitor cells (NPCs).
Here, we identify coordinated adaptations in NPC biology that bias neurodevelopmental trajectories toward neocortical downscaling.
By combining marmoset and human cerebral organoids with analyses of fetal marmoset neocortical tissue and previously published histological data, we uncover multiple adaptations in apical and basal progenitors that converge on reduced progenitor capacity, alter early progenitor dynamics, and likely constrain neuronal output, thereby limiting the size and folding of the marmoset neocortex.
