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Sci Rep. 2017 Mar 7;7:43093. doi: 10.1038/srep43093.

Nkx2.1 regulates the generation of telencephalic astrocytes during embryonic development.

Author information

1
Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
2
Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Av. de France 15, CH-1004 Lausanne, Switzerland.
3
Department of Psychiatry, Center for Psychiatric Neuroscience, Lausanne University Hospital, Prilly, CH-1008 Lausanne, Switzerland.

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.

PMID:
28266561
PMCID:
PMC5339799
DOI:
10.1038/srep43093
[Indexed for MEDLINE]
Free PMC Article

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