4.8 Article

Localized astrogenesis regulates gyrification of the cerebral cortex

Journal

SCIENCE ADVANCES
Volume 8, Issue 10, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abi5209

Keywords

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Funding

  1. Ministry of Education, Culture, Sports, Science and Technology (MEXT)
  2. Takeda Science Foundation
  3. Uehara Memorial Foundation
  4. Naito Foundation
  5. European Research Council (ERC) Starting Grant [281961 AstroFunc]
  6. European Commission Horizon 2020 Action [NCBio 951923]
  7. European Commission [FP7-PEOPLE-2012-IEF 331018 PlasticAstros]
  8. Kanazawa University SAKIGAKE Project
  9. Kanazawa University CHOZEN Project

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This study reveals the important role of localized astrogenesis in gyrus formation in the mammalian brain. The findings suggest that the positive feedback loop of FGF signaling is a crucial mechanism underlying cortical folding.
The development and evolution of mammalian higher cognition are represented by gyrification of the laminar cerebral cortex and astrocyte development, but their mechanisms and interrelationships remain unknown. Here, we show that localized astrogenesis plays an important role in gyri formation in the gyrencephalic cerebral cortex. In functional genetic experiments, we show that reducing astrocyte number prevents gyri formation in the ferret cortex, while increasing astrocyte number in mice, which do not have cortical folds, can induce gyrus-like protrusions. Morphometric analyses demonstrate that the vertical expansion of deep pallial regions achieved by localized astrogenesis is crucial for gyri formation. Furthermore, our findings suggest that localized astrogenesis by a positive feedback loop of FGF signaling is an important mechanism underlying cortical folding in gyrencephalic mammalian brains. Our findings reveal both the cellular mechanisms and the mechanical principle of gyrification in the mammalian brain.

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