title: Nkx2.1 regulates the generation of telencephalic astrocytes during embryonic development.
abstract: The homeodomain transcription factor Nkx2.1 (NK2 homeobox 1) controls cell differentiation of telencephalic GABAergic interneurons and oligodendrocytes. Here we show that Nkx2.1 also regulates astrogliogenesis of the telencephalon from embryonic day (E) 14.5 to E16.5. Moreover we identify the different mechanisms by which Nkx2.1 controls the telencephalic astrogliogenesis. In Nkx2.1 knockout (Nkx2.1-/-) mice a drastic loss of astrocytes is observed that is not related to cell death. Further, in vivo analysis using BrdU incorporation reveals that Nkx2.1 affects the proliferation of the ventral neural stem cells that generate early astrocytes. Also, in vitro neurosphere assays showed reduced generation of astroglia upon loss of Nkx2.1, which could be due to decreased precursor proliferation and possibly defects in glial specification/differentiation. Chromatin immunoprecipitation analysis and in vitro co-transfection studies with an Nkx2.1-expressing plasmid indicate that Nkx2.1 binds to the promoter of glial fibrillary acidic protein (GFAP), primarily expressed in astrocytes, to regulate its expression. Hence, Nkx2.1 controls astroglial production spatiotemporally in embryos by regulating proliferation of the contributing Nkx2.1-positive precursors.
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Minocha
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
authors.forename: Delphine
authors.initials: D
authors.lastname: Valloton
authors.affiliation: Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Av. de France 15, CH-1004 Lausanne, Switzerland.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Arsenijevic
authors.affiliation: Department of Psychiatry, Center for Psychiatric Neuroscience, Lausanne University Hospital, Prilly, CH-1008 Lausanne, Switzerland.
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Cardinaux
authors.affiliation: Department of Psychiatry, Center for Psychiatric Neuroscience, Lausanne University Hospital, Prilly, CH-1008 Lausanne, Switzerland.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Guidi
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hornung
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
authors.forename: Cécile
authors.initials: C
authors.lastname: Lebrand
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D013687:Telencephalon / Q000378:metabolism* / Q000502:physiology; D000074482:Thyroid Nuclear Factor 1 / Q000378:metabolism / Q000502:physiology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D000074482:Thyroid Nuclear Factor 1