title: 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.
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Shukun
authors.initials: S
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Baoguo
authors.initials: B
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Qiao
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lv
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Qingli
authors.initials: Q
authors.lastname: Liang
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zixiao
authors.initials: Z
authors.lastname: Shi
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Xia
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Ji
authors.affiliation: The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China jwjiao@ioz.ac.cn.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jiao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D002454:Cell Differentiation / Q000235:genetics*; D002525:Cerebellar Cortex / Q000254:growth & development* / Q000378:metabolism; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D055495:Neurogenesis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D050796:STAT3 Transcription Factor; C491409:Socs2 protein, mouse; C494087:Stat3 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
keywords: astrocyte differentiation; autophagy; cortical development