Nwd1 regulates neuronal differentiation and migration through purinosome formation in the developing cerebral cortex

Seiya Yamada, Ayaka Sato, Shin ichi Sakakibara

Research output: Contribution to journalArticlepeer-review

Abstract

Engagement 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 catalyze de novo purine 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.

Original languageEnglish
JournalUnknown Journal
DOIs
Publication statusPublished - 2019 Dec 16

Keywords

  • Fgams
  • neural stem/progenitor cells
  • neuronal differentiation
  • neuronal migration
  • Nwd1
  • Paics
  • purines
  • purinosome
  • signal transduction ATPases with numerous domains

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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