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Nwd1 Regulates Neuronal Differentiation and Migration Through Purinosome Formation in the Developing Cerebral Cortex

68 Pages Posted: 5 Jan 2020 Sneak Peek Status: Review Complete

See all articles by Seiya Yamada

Seiya Yamada

Waseda University, Graduate School of Human Sciences, Laboratory for Molecular Neurobiology

Ayaka Sato

Waseda University, Graduate School of Human Sciences, Laboratory for Molecular Neurobiology

Shin-ichi Sakakibara

Waseda University, Graduate School of Human Sciences, Laboratory for Molecular Neurobiology

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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 d omain-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.

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

Suggested Citation

Yamada, Seiya and Sato, Ayaka and Sakakibara, Shin-ichi, Nwd1 Regulates Neuronal Differentiation and Migration Through Purinosome Formation in the Developing Cerebral Cortex (December 27, 2019). ISCIENCE-D-19-01529. Available at SSRN: https://ssrn.com/abstract=3510211 or http://dx.doi.org/10.2139/ssrn.3510211
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Seiya Yamada

Waseda University, Graduate School of Human Sciences, Laboratory for Molecular Neurobiology ( email )

Saitama
Japan

Ayaka Sato

Waseda University, Graduate School of Human Sciences, Laboratory for Molecular Neurobiology

Saitama
Japan

Shin-ichi Sakakibara (Contact Author)

Waseda University, Graduate School of Human Sciences, Laboratory for Molecular Neurobiology ( email )

Saitama
Japan

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