A Sox1 to Pax6 switch drives neuroectoderm to radial glia progression during differentiation of mouse embryonic stem cells.
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.
Suter
David M
DM
Department of Pathology and Immunology, University of Geneva Medical School, Switzerland.
Tirefort
Diderik
D
Julien
Stephanie
S
Krause
Karl-Heinz
KH
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005818:Genetic Engineering; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D054258:Neural Plate / Q000166:cytology* / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*
D015415:Biomarkers; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse