The determination of projection neuron identity in the developing cerebral cortex

Curr Opin Neurobiol. 2008 Feb;18(1):28-35. doi: 10.1016/j.conb.2008.05.006. Epub 2008 May 26.


Here we review the mechanisms that determine projection neuron identity during cortical development. Pyramidal neurons in the mammalian cerebral cortex can be classified into two major classes: corticocortical projection neurons, which are concentrated in the upper layers of the cortex, and subcortical projection neurons, which are found in the deep layers. Early progenitor cells in the ventricular zone produce deep layer neurons that express transcription factors including Sox5, Fezf2, and Ctip2, which play important roles in the specification of subcortically projecting axons. Upper layer neurons are produced from progenitors in the subventricular zone, and the expression of Satb2 in these differentiating neurons is required for the formation of axonal projections that connect the two cerebral hemispheres. The Fezf2/Ctip2 and Satb2 pathways appear to be mutually repressive, thus ensuring that individual neurons adopt either a subcortical or callosal projection neuron identity at early times during development. The molecular mechanisms by which Satb2 regulates gene expression involves long-term epigenetic changes in chromatin configuration, which may enable cell fate decisions to be maintained during development.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cell Proliferation
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism*
  • Efferent Pathways / cytology
  • Efferent Pathways / embryology
  • Efferent Pathways / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Humans
  • Phenotype
  • Pyramidal Cells / cytology
  • Pyramidal Cells / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Transcription Factors