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标题：Nwd1 Regulates Neuronal Differentiation and Migration through Purinosome Formation in the Developing Cerebral Cortex
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作者：Seiya Yamada ; Ayaka Sato ; Shin-ichi Sakakibara 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：5
页码：1-46
DOI：10.1016/j.isci.2020.101058
语种：English
出版社：Elsevier
摘要：SummaryEngagement of neural stem/progenitor cells (NSPCs) into proper neuronal differentiation requires the spatiotemporally regulated generation of metabolites. Purines are essential building blocks for many signaling molecules. Enzymes that catalyzede novopurine synthesis are assembled as a huge multienzyme complex called “purinosome.” However, there is no evidence of the formation or physiological function of the purinosome in the brain. Here, we showed that a signal transduction ATPases with numerous domains (STAND) protein, NACHT and WD repeat domain-containing 1 (Nwd1), interacted with Paics, a purine-synthesizing enzyme, to regulate purinosome assembly in NSPCs. Altered Nwd1 expression affected purinosome formation and induced the mitotic exit and premature differentiation of NSPCs, repressing neuronal migration and periventricular heterotopia. Overexpression/knockdown of Paics or Fgams, other purinosome enzymes, in the developing brain resulted in a phenocopy of Nwd1 defects. These findings indicate that strict regulation of purinosome assembly/disassembly is crucial for maintaining NSPCs and corticogenesis.Graphical AbstractDisplay OmittedHighlights•STAND protein Nwd1 interacts with Paics to regulate the purinosome formation•Dysregulated expression of Nwd1 induced the premature differentiation of NSPCs•Nwd1 KD repressed the neuronal migration, causing the periventricular heterotopia•Tightly regulated assembly of purinosome components is crucial for corticogenesisDevelopmental Neuroscience; Cellular Neuroscience; Stem Cells Research