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Scientific article
English

A Sox1 to Pax6 switch drives neuroectoderm to radial glia progression during differentiation of mouse embryonic stem cells

Published inStem cells, vol. 27, no. 1, p. 49-58
Publication date2009
Abstract

The transcription factors Sox1 and Pax6 are expressed sequentially during early mouse embryonic neurogenesis. Sox1 expression starts upon formation of neuroectoderm, whereas Pax6 is subsequently expressed in radial glial cells, the latter giving rise to most neurons of the cerebral cortex. Here we used mouse embryonic stem (ES) cells to study the role of Sox1 and Pax6 in regulating differentiation of neural progenitors. For this purpose, we investigated the effect of overexpression and knockdown of Sox1 and Pax6, using three differentiation protocols. We show that (a) expression of Sox1 or Pax6 in uncommitted ES cells favored neuroectodermal lineage choice; (b) continuous Sox1 expression maintained cells at the neuroepithelial stage and prevented expression of Pax6 and other radial glial cell markers; (c) Sox1 knockdown facilitated exit from the progenitor stage, whereas Pax6 knockdown decreased formation of radial glia; (d) forced Pax6 expression in neuroepithelial cells triggered their differentiation into radial glia and neurons; and (e) Pax6 expression induced cell migration, a feature typical of radial glia-derived early neurons. We conclude that Sox1 enhances neuroectodermal commitment and maintenance but blocks further differentiation. In contrast, Pax6 is involved in the progression of neuroectoderm toward radial glia.

Keywords
  • Animals
  • Biological Markers/metabolism
  • Cell Differentiation
  • Cell Line
  • Cell Movement
  • Embryo, Mammalian/cytology
  • Embryonic Stem Cells/ cytology/metabolism
  • Eye Proteins/ metabolism
  • Gene Knockdown Techniques
  • Genetic Engineering
  • Homeodomain Proteins/ metabolism
  • Mice
  • Models, Biological
  • Neural Plate/ cytology/metabolism
  • Neuroepithelial Cells/cytology/metabolism
  • Neuroglia/ cytology/metabolism
  • Neurons/cytology/metabolism
  • Paired Box Transcription Factors/ metabolism
  • RNA, Small Interfering/metabolism
  • Repressor Proteins/ metabolism
  • SOXB1 Transcription Factors/ metabolism
Affiliation Not a UNIGE publication
Citation (ISO format)
SUTER, D. M. et al. A Sox1 to Pax6 switch drives neuroectoderm to radial glia progression during differentiation of mouse embryonic stem cells. In: Stem cells, 2009, vol. 27, n° 1, p. 49–58. doi: 10.1634/stemcells.2008-0319
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accessLevelRestricted
Identifiers
ISSN of the journal1066-5099
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