serval:BIB_9901DB8C1BCE
Nkx2.1 regulates the generation of telencephalic astrocytes during embryonic development.
10.1038/srep43093
000395585900001
28266561
Minocha
S.
author
Valloton
D.
author
Arsenijevic
Y.
author
Cardinaux
J.R.
author
Guidi
R.
author
Hornung
J.P.
author
Lebrand
C.
author
article
2017-03-07
Scientific reports
2045-2322
2045-2322
journal
7
43093
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.
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
eng
60_published
true
peer-reviewed
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
University of Lausanne
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