Marmoset organoids trace the unfolded cortex to progenitors that divide slowly and stop early

The number of neurons a developing brain produces is one of the decisive factors in how large and how folded it becomes ^[6]. In the human brain, those grooves and ridges expand the surface area enough to hold billions of nerve cells ^[19]. So a question about brain shape turns into a question about the cells upstream of the neurons, and the German Primate Center group reported differences in three separate properties of those cells: how fast they divide, what shape they take, and how long they keep dividing quickly ^[20].

Speed and shape came first. "Our investigations have shown that certain progenitor cells in the common marmoset divide significantly more slowly than in humans," said Cesar Mateo Bastidas Betancourt, one of the study's two first authors ^[7][22]. "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," he said ^[8]. The release does not give a figure for how much slower that division is ^[21].

Then the schedule. Marmoset progenitors have a shorter overall window in which they can proliferate rapidly ^[9]. "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," said Lidiia Tynianskaia, the other first author ^[10][22].

Most of the work ran in organoids, which the group says reproduce the timing of certain developmental stages accurately ^[13], and the key results were then rechecked in fetal brain tissue ^[14]. "The study combines the advantages of in vivo and in vitro methods," said Michael Heide, who heads the junior research group ^[15][22].

The organoids cannot show whether human cortical folding disorders involve the same cellular properties, and no disorder was studied here. The DPZ says the work could help improve understanding of developmental disorders in the human brain in future ^[16]. That is a direction for later experiments. The measured quantities are division rate, progenitor morphology and proliferative window ^[4]; the smooth cortex belongs to the animal ^[1], and the step from fewer neurons to fewer folds is the authors' inference ^[8].

One reason the marmoset case is informative for evolution: researchers now believe that even the common ancestor of all primates had a medium-sized and at least partially folded brain ^[17]. That makes the smooth marmoset cortex a later change in a lineage that had folding available. The species is increasingly used in biomedical research ^[18].