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  4. Interspecific diversity in the neuronal composition of the mammalian cortex arises from heterochrony in neurogenesis

Interspecific diversity in the neuronal composition of the mammalian cortex arises from heterochrony in neurogenesis

Journal EMBO J. (2026)
Title Interspecific diversity in the neuronal composition of the mammalian cortex arises from heterochrony in neurogenesis
Laboratory Laboratory of functional genomics for human evolution〈Prof. SUZUKI K. Ikuo〉
Abstract

Mammals share a laminar cerebral cortex, with excitatory neuron subtypes organized in distinct layers. Although this framework is conserved, subtype balance varies markedly between species due to unknown mechanisms. This study shows that species-specific neuronal composition arises from non-uniform scaling of the temporal dynamics of neurogenesis. Comparative histology of eight mammalian species revealed a significant, rat-specific expansion of the cortical deeper layer (DL). This species difference results from a specific extension of the early neurogenetic phase for DL neuron production before transitioning to the upper layer (UL) in rats, as confirmed by birthdating and single-cell transcriptomics. The duration of DL neuron production is regulated by a genetic program controlling progenitor aging, including canonical Wnt signaling. Comparative single-cell transcriptomics revealed that cortical progenitors in rats exhibit significantly elevated Wnt ligand expression. Thus, while sequential cortical neurogenesis is conserved, its progression is non-uniformly scaled in each species. Such precise heterochronic fine-tuning allows evolutionary refinement of cellular configuration without drastic remodeling of the conserved corticogenesis program.

Authors

Yuki Y. Yamauchi (1, 12), Xuanhao D. Sheu (1, 12), Rafat Tarfder (2), Takuma Kumamoto (3), Jun Hatakeyama (4), Haruka Sato (4), Pauline Rouillard (2), Merve Bilgic (5), Shuto Deguchi (6, 7), Tomonori Nakamura (6, 7, 8), Yusuke Kishi (5, 9, 10), Kazuo Emoto (2, 11), and Ikuo K. Suzuki (1)


  1. Laboratory of functional genomics for human evolution, Graduate School of Frontier Biosciences, The University of Osaka.
  2. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  3. Developmental Neuroscience Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
  4. Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
  5. Laboratory of Molecular Neurobiology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
  6. Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
  7. Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  8. The Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan.
  9. Laboratory of Molecular Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  10. Division of Aging Biology, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan.
  11. International Research Center for Neurointelligence, The University of Tokyo, Tokyo, Japan.
  12. These authors contributed equally: Yuki Y Yamauchi, Xuanhao D Sheu.

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