title: Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone.
abstract: Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thus, our work uncovers a novel function of Prox1 as a fate determinant for oligodendrocytes in the adult mammalian brain. These data indicate that the neurogenic and oligodendrogliogenic lineages in the two adult neurogenic niches exhibit a distinct requirement for Prox1, being important for neurogenesis in the DG but being indispensable for oligodendrogliogenesis in the SVZ. Stem Cells 2016;34:2115-2129.
authors.affiliation: Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Bunk
authors.affiliation: Computational Biology, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.|Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Ertaylan
authors.affiliation: Institute of Physiological Chemistry and the Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.|Department of Biochemistry and Molecular Biology IV, Faculty of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Ortega
authors.affiliation: Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany.|Developmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pavlou
authors.affiliation: Computational Biology, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
authors.forename: Laura
authors.initials: L
authors.lastname: Gonzalez Cano
authors.affiliation: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Stergiopoulos
authors.affiliation: Max Planck Institute for Experimental Medicine, Göttingen, Germany.
authors.forename: Shima
authors.initials: S
authors.lastname: Safaiyan
authors.affiliation: Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Völs
authors.affiliation: Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: van Cann
authors.affiliation: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Greece.
authors.forename: Panagiotis K
authors.initials: PK
authors.lastname: Politis
authors.affiliation: Max Planck Institute for Experimental Medicine, Göttingen, Germany.|Department of Neurology, University of Göttingen, Göttingen, Germany.
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
authors.affiliation: Institute of Physiological Chemistry and the Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Berninger
authors.affiliation: Computational Biology, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
authors.forename: Antonio
authors.initials: A
authors.lastname: Del Sol
authors.affiliation: Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany.|Developmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schwamborn
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000378:metabolism*; D020547:Lateral Ventricles / Q000166:cytology*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2 / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; C512773:Olig2 protein, mouse; D000076104:Oligodendrocyte Transcription Factor 2; D051880:Receptors, Notch; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
keywords: Adult neurogenesis; Neural stem cells; Oligodendrocytes; Prox1