Open AccessSox1 Maintains the Undifferentiated State of Cortical Neural Progenitor Cells via the Suppression of Prox1‐Mediated Cell Cycle Exit and Neurogenesis
Author(s) -
Elkouris Maximilianos,
Balaskas Nikos,
Poulou Maria,
Politis Panagiotis K.,
Panayiotou Elena,
Malas Stavros,
Thomaidou Dimitra,
Remboutsika Eumorphia
Publication year - 2011
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 - 10.1002/stem.554
Subject(s) - neurogenesis , biology , progenitor cell , microbiology and biotechnology , neural stem cell , cell cycle , stem cell , cellular differentiation , progenitor , cell , genetics , gene
Neural stem/progenitor cells maintain their identity via continuous self‐renewal and suppression of differentiation. Gain‐of‐function experiments in the chick revealed an involvement for Sox1‐3 transcription factors in the maintenance of the undifferentiated neural progenitor (NP) identity. However, the mechanism(s) employed by each factor has not been resolved. Here, we derived cortical neural/stem progenitor cells from wild‐type and Sox1 ‐null mouse embryos and found that Sox1 plays a key role in the suppression of neurogenic cell divisions. Loss of Sox1 leads to progressive depletion of self‐renewing cells, elongation of the cell cycle of proliferating cells, and significant increase in the number of cells exiting the cell cycle. In proliferating NP cells, Sox1 acts via a prospero‐related homeobox 1 (Prox1)‐mediated pathway to block cell cycle exit that leads to neuronal differentiation in vivo and in vitro. Thus, our results demonstrate that Sox1 regulates the size of the cortical NP pool via suppression of Prox1‐mediated neurogenic cell divisions. S TEM C ELLS 2011;29:89–98