title: Sox1 maintains the undifferentiated state of cortical neural progenitor cells via the suppression of Prox1-mediated cell cycle exit and neurogenesis.
abstract: 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.
authors.affiliation: Stem Cell Biology Laboratory, Institute of Molecular Biology and Genetics, Vari-Attica, Greece.
authors.forename: Maximilianos
authors.initials: M
authors.lastname: Elkouris
authors.forename: Nikos
authors.initials: N
authors.lastname: Balaskas
authors.forename: Maria
authors.initials: M
authors.lastname: Poulou
authors.forename: Panagiotis K
authors.initials: PK
authors.lastname: Politis
authors.forename: Elena
authors.initials: E
authors.lastname: Panayiotou
authors.forename: Stavros
authors.initials: S
authors.lastname: Malas
authors.forename: Dimitra
authors.initials: D
authors.lastname: Thomaidou
authors.forename: Eumorphia
authors.initials: E
authors.lastname: Remboutsika
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000032:analysis; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D055879:Gene Knock-In Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D001973:Bromodeoxyuridine