Abstract
Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression of GFAP, a marker of terminally differentiated astrocytes. However, astrocyte specification occurs before GFAP expression and essential factors for the specification step have remained elusive. Here we show that Zbtb20 regulates astrocyte specification in the mouse neocortex. Zbtb20 is highly expressed in late-stage NPCs and their astrocytic progeny. Overexpression and knockdown of Zbtb20 promote and suppress astrocytogenesis, respectively, although Zbtb20 does not directly activate the Gfap promoter. Astrocyte induction by Zbtb20 is suppressed by knockdown of Sox9 or NFIA. Furthermore, in the astrocyte lineage, Zbtb20 directly represses the expression of Brn2, which encodes a protein necessary for upper-layer neuron specification. Zbtb20 is thus a key determinant of astrocytogenesis, in which it collaborates with Sox9 and NFIA, and acts in part through direct repression of Brn2 expression.
Highlights
Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development
Neocortical NPCs isolated at E11.5 and cultured for 3 or 9 days in vitro (DIV) correspond to neurogenic and gliogenic stages, respectively[29], and we found that the abundance of Zbtb[20] messenger RNA was higher in 9 DIV cultures than in 3 DIV cultures (Fig. 1c)
(b,c) Quantitative reverse transcriptase–PCR (RT–PCR) analysis of relative Zbtb[20] mRNA abundance in the ventricular zone (VZ)/subventricular zone (SVZ) of the embryonic forebrain (b) and in NPCs cultured with Fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) for 3 or 9 DIV (c)
Summary
Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression of GFAP, a marker of terminally differentiated astrocytes. Previous studies of astrocytogenesis have relied primarily on the induction of glial fibrillary acidic protein (GFAP) expression as a marker of terminal astrocyte differentiation[4,5,6,7,8] and have shown that the JAK-STAT and Smad pathways directly regulate the promoter of the GFAP gene[10,11,15]. The transcription factors Sox[9] and nuclear factor I/A (NFIA) are implicated in astrocyte specification in the embryonic spinal cord[16,17,18,19] These molecules are expressed in cells of the oligodendrocyte lineage[17,19,20]. We hypothesized that some other molecule or mechanism essential for astrocyte specification remains to be discovered
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
