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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_9901DB8C1BCE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nkx2.1 regulates the generation of telencephalic astrocytes during embryonic development.
Journal
Scientific reports
Author(s)
Minocha S., Valloton D., Arsenijevic Y., Cardinaux J.R., Guidi R., Hornung J.P., Lebrand C.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
07/03/2017
Peer-reviewed
Oui
Volume
7
Pages
43093
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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 <sup>-/-</sup> ) 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.
Keywords
Animals, Astrocytes/metabolism, Astrocytes/physiology, Cell Differentiation, Embryonic Development, Gene Expression Regulation, Developmental, Glial Fibrillary Acidic Protein/genetics, Mice, Mice, Knockout, Telencephalon/metabolism, Telencephalon/physiology, Thyroid Nuclear Factor 1/metabolism, Thyroid Nuclear Factor 1/physiology
Pubmed
Web of science
Open Access
Yes
Create date
14/03/2017 11:44
Last modification date
05/03/2020 7:20
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