Researchers from The University of Osaka found that the timing of signaling pathways during brain development leads to differences in brain structure among related species

Osaka, Japan – The outer regions of the brain, the cortex, have specific layers of different cells – neurons – that are similarly ordered among all mammals, from tiny mouse brains to huge elephant brains. However, the proportions of different cell layers vary widely among species, and little is known about how and why this variation happens.

Now, researchers from The University of Osaka have suggested, following intense research on developing brain cells, that these differences are related to the timing of specific signals in the brain during early development. These findings have been published in The EMBO Journal.

The research team began their investigation by focusing specifically on the rat cortex, noting that rats had a much larger deep layer – relative to the upper cortical layer – than seven other mammals, including mice.

Following this initial discovery the brains of rats were compared with those of mice – their closest evolutionary relative – in more detail. The research subsequently reported that this difference was due to the greater numbers of deep layer neurons present, rather than just a larger layer area.

“We next wanted to see how this difference in the number of deep layer neuron arises,” says Yuki Yamauchi, lead author of the study. “Using a cell-labeling technique in rats and mice, we saw that rat neural progenitor cells produced more deep layer neurons.”

A neural progenitor cell is a type of stem cell that generates neurons while the brain is still developing. To understand why rat brains create more deep layer neurons in early development, the timing of upper and deep layer neuron production in mice and rats was assessed.

Interestingly, mice produced deep layer neurons for one or two days before the progenitor cells switched to producing upper layer neurons, whereas rats produced deep layer neurons for around four days before making this switch.

This difference between rats and mice is likely caused by different timing of the expression of molecules involved in Wnt signaling, a process that is already known to be important for regulating the timing of cortical development. Wnt glycoproteins are key for enacting various cell processes, and rats had prolonged expression of Wnt signaling genes, leading to extended deep layer neuron production.

“As well as highlighting the unusual cortical structure of rats relative to other mammals, we demonstrated that this variation arises from the distinct ‘aging rates’ of neural progenitor cells,” notes senior author of the study Ikuo Suzuki. “This finding broadens our understanding of the different mechanisms underlying divergent brain structure among related species.”

These findings from the developing rat cortex will contribute to a deeper understanding of human brain evolution. In turn, this may also help broaden our knowledge of the mechanisms underlying developmental and neurological disorders, with exciting potential applications in regenerative medicine.

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The article, “Interspecific diversity in the neuronal composition of the mammalian cortex arises from heterochrony in neurogenesis,” was published in The EMBO Journal at DOI: https://doi.org/10.1038/s44318-026-00806-z

About The University of Osaka
The University of Osaka was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, The University of Osaka is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Website: https://resou.osaka-u.ac.jp/en