Zbtb20 promotes astrocytogenesis during neocortical development.
Zbtb20 promotes astrocytogenesis during neocortical development.
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DOI：
10.1038/ncomms11102
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发表时间：
2016-03-22
影响因子：
16.6
通讯作者：
Gotoh Y
中科院分区：
文献类型：
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作者：
Nagao M;Ogata T;Sawada Y;Gotoh Y
多能神经前体细胞（NPC）在哺乳动物新皮层发育的后期产生星形胶质细胞。许多调节星形胶质细胞发生的信号通路直接诱导终末分化星形胶质细胞的标志物GFAP的表达。然而，星形胶质细胞的规范发生在GFAP表达之前，规范步骤的基本因素仍然难以捉摸。在这里，我们表明，Zbtb20调节小鼠新皮层中的星形胶质细胞特化。Zbtb20在晚期NPC及其星形胶质细胞后代中高度表达。Zbtb20的过表达和敲低分别促进和抑制星形细胞发生，尽管Zbtb20不直接激活GFAP启动子。Zbtb20对星形胶质细胞的诱导可通过敲低Sox9或NFIA而抑制。此外，在星形胶质细胞谱系中，Zbtb20直接抑制Brn2的表达，Brn2编码上层神经元特化所必需的蛋白质。因此，Zbtb20是星形胶质细胞发生的关键决定因素，其中它与Sox 9和NFIA合作，并部分通过直接抑制Brn2表达发挥作用。 脑中的星形胶质细胞来源于神经前体细胞（NPC）。在这里，Motoshi Nagao及其同事表明转录抑制子Zbtb20调节小鼠新皮层中的星形胶质细胞特化。
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. Astrocytes in the brain are derived from neural precursor cells (NPCs). Here, Motoshi Nagao and colleagues show that the transcription repressor Zbtb20 regulates astrocyte specification in the mouse neocortex.