An intrinsic mechanism of corticogenesis from embryonic stem cells

Nature. 2008 Sep 18;455(7211):351-7. doi: 10.1038/nature07287. Epub 2008 Aug 17.

Abstract

The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / physiology
  • Cell Differentiation* / drug effects
  • Cell Lineage / drug effects
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / embryology*
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects
  • Mice
  • Pyramidal Cells / drug effects
  • Veratrum Alkaloids / pharmacology

Substances

  • Veratrum Alkaloids
  • cyclopamine