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Autophagy-related gene Atg5 is essential for astrocyte differentiation in the developing mouse cortex.


ABSTRACT: Astrocyte differentiation is essential for late embryonic brain development, and autophagy is active during this process. However, it is unknown whether and how autophagy regulates astrocyte differentiation. Here, we show that Atg5, which is necessary for autophagosome formation, regulates astrocyte differentiation. Atg5 deficiency represses the generation of astrocytes in vitro and in vivo. Conversely, Atg5 overexpression increases the number of astrocytes substantially. We show that Atg5 activates the JAK2-STAT3 pathway by degrading the inhibitory protein SOCS2. The astrocyte differentiation defect caused by Atg5 loss can be rescued by human Atg5 overexpression, STAT3 overexpression, and SOCS2 knockdown. Together, these data demonstrate that Atg5 regulates astrocyte differentiation, with potential implications for brain disorders with autophagy deficiency.

SUBMITTER: Wang S 

PROVIDER: S-EPMC4253845 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Autophagy-related gene Atg5 is essential for astrocyte differentiation in the developing mouse cortex.

Wang Shukun S   Li Baoguo B   Qiao Huimin H   Lv Xiaohui X   Liang Qingli Q   Shi Zixiao Z   Xia Wenlong W   Ji Fen F   Jiao Jianwei J  

EMBO reports 20140915 10


Astrocyte differentiation is essential for late embryonic brain development, and autophagy is active during this process. However, it is unknown whether and how autophagy regulates astrocyte differentiation. Here, we show that Atg5, which is necessary for autophagosome formation, regulates astrocyte differentiation. Atg5 deficiency represses the generation of astrocytes in vitro and in vivo. Conversely, Atg5 overexpression increases the number of astrocytes substantially. We show that Atg5 activ  ...[more]

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