Nkx2.1 regulates the proliferation and cell fate of telencephalic astrocytes during embryonic development

The homeodomain transcription factor Nkx2.1 controls cell differentiation of telencephalic GABAergic interneurons and oligodendrocytes. Here, we show that Nkx2.1 additionally regulates astrogliogenesis of the telencephalon from embryonic day (E) 14.5 to E16.5. Our work aims to identify the different mechanisms by which Nkx2.1 controls telencephalic astrogliogenesis. In Nkx2.1 -/- , a drastic loss of astrocytes is observed which is not related to cell death. In vivo analysis using BrdU incorporation reveals that Nkx2.1 affects the proliferation of ventral neural stem cells that generate early astrocytes. In vitro neurosphere assays show that Nkx2.1 additionally affects the differentiation step of Nkx2.1-derived astrocytes. Chromatin immunoprecipitation and in vitro co-transfection studies of a Nkx2.1-expressing plasmid indicate that Nkx2.1 binds to the promoter of astroglial differentiation gene GFAP, and regulates its expression. Hence, Nkx2.1 controls astroglial production spatiotemporally in embryos by regulating stem cell division and specification of the contributing Nkx2.1 + precursors.