Regulation of cerebral cortex size and folding by expansion of basal progenitors

Miki Nonaka-Kinoshita, Isabel Reillo, Benedetta Artegiani, Maria Ángeles Martínez-Martínez, Mark Nelson, Víctor Borrell, Federico Calegari

Research output: Contribution to journalArticlepeer-review

171 Citations (Scopus)


Size and folding of the cerebral cortex increased massively during mammalian evolution leading to the current diversity of brain morphologies. Various subtypes of neural stem and progenitor cells have been proposed to contribute differently in regulating thickness or folding of the cerebral cortex during development, but their specific roles have not been demonstrated. We report that the controlled expansion of unipotent basal progenitors in mouse embryos led to megalencephaly, with increased surface area of the cerebral cortex, but not to cortical folding. In contrast, expansion of multipotent basal progenitors in the naturally gyrencephalic ferret was sufficient to drive the formation of additional folds and fissures. In both models, changes occurred while preserving a structurally normal, six-layered cortex. Our results are the first experimental demonstration of specific and distinct roles for basal progenitor subtypes in regulating cerebral cortex size and folding during development underlying the superior intellectual capability acquired by higher mammals during evolution.

Original languageEnglish
Pages (from-to)1817-28
Number of pages12
JournalThe EMBO journal
Issue number13
Publication statusPublished - 3 Jul 2013
Externally publishedYes


  • Animals
  • Brain/cytology
  • Cell Differentiation
  • Cells, Cultured
  • Cerebral Cortex/cytology
  • Embryo, Mammalian/cytology
  • Ferrets
  • Immunoenzyme Techniques
  • Intermediate Filament Proteins/physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins/physiology
  • Nestin
  • Stem Cells/cytology


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