Gyrification of the cerebral cortex requires FGF signaling in the mammalian brain

Elife. 2017 Nov 14:6:e29285. doi: 10.7554/eLife.29285.


Although it has been believed that the evolution of cortical folds was a milestone, allowing for an increase in the number of neurons in the cerebral cortex, the mechanisms underlying the formation of cortical folds are largely unknown. Here we show regional differences in the expression of fibroblast growth factor receptors (FGFRs) in the developing cerebral cortex of ferrets even before cortical folds are formed. By taking the advantage of our in utero electroporation technique for ferrets, we found that cortical folding was impaired in the ferret cerebral cortex when FGF signaling was inhibited. We also found that FGF signaling was crucial for producing Pax6-positive neural progenitors in the outer subventricular zone (OSVZ) of the developing cerebral cortex. Furthermore, we found that upper layers of the cerebral cortex were preferentially reduced by inhibiting FGF signaling. Our results shed light on the mechanisms of cortical folding in gyrencephalic mammalian brains.

Keywords: cerebral cortex; fibroblast growth factor; gyrus; in utero electroporation; neuroscience; outer subventricular zone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cerebral Cortex / embryology*
  • Ferrets
  • Fibroblast Growth Factors / metabolism
  • Neural Stem Cells / physiology
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Signal Transduction*


  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.