Open AccessA Sox1 to Pax6 Switch Drives Neuroectoderm to Radial Glia Progression During Differentiation of Mouse Embryonic Stem Cells
Author(s) -
Suter David M.,
Tirefort Diderik,
Julien Stephanie,
Krause KarlHeinz
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0319
Subject(s) - neuroectoderm , pax6 , biology , neuroepithelial cell , neurogenesis , embryonic stem cell , neural stem cell , microbiology and biotechnology , cellular differentiation , progenitor cell , gene knockdown , stem cell , mesoderm , genetics , transcription factor , cell culture , gene
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. S TEM C ELLS 2009;27:49–58