FBXL5 inactivation in mouse brain induces aberrant proliferation of neural stem progenitor cells

Takayoshi Yamauchi, Masaaki Nishiyama, Toshiro Moroishi, Atsuki Kawamura, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

FBXL5 is the substrate recognition subunit of an SCF-type ubiquitin ligase that serves as a master regulator of iron metabolism in mammalian cells. We previously showed that mice with systemic deficiency of FBXL5 fail to sense intracellular iron levels and die in utero at embryonic day 8.5 (E8.5) as a result of iron overload and subsequent oxidative stress. This early embryonic mortality has thus impeded study of the role of FBXL5 in brain development. We have now generated mice lacking FBXL5 specifically in nestin-expressing neural stem progenitor cells (NSPCs) in the brain. Unexpectedly, the mutant embryos manifested a progressive increase in the number of NSPCs and astroglia in the cerebral cortex. Stabilization of iron regulatory protein 2 (IRP2) as a result of FBXL5 deficiency led to accumulation of ferrous and ferric iron as well as to generation of reactive oxygen species. Pharmacological manipulation suggested that the phenotypes of FBXL5 deficiency are attributable to aberrant activation of mammalian target of rapamycin (mTOR) signaling. Our results thus show that FBXL5 contributes to regulation of NSPC proliferation during mammalian brain development.

元の言語英語
記事番号e00470-16
ジャーナルMolecular and cellular biology
37
発行部数8
DOI
出版物ステータス出版済み - 4 1 2017

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Neural Stem Cells
Stem Cells
Iron
Iron Regulatory Protein 2
Brain
SKP Cullin F-Box Protein Ligases
Nestin
Iron Overload
Sirolimus
Astrocytes
Cerebral Cortex
Reactive Oxygen Species
Oxidative Stress
Embryonic Structures
Cell Proliferation
Pharmacology
Phenotype
Mortality

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

これを引用

FBXL5 inactivation in mouse brain induces aberrant proliferation of neural stem progenitor cells. / Yamauchi, Takayoshi; Nishiyama, Masaaki; Moroishi, Toshiro; Kawamura, Atsuki; Nakayama, Keiichi I.

:: Molecular and cellular biology, 巻 37, 番号 8, e00470-16, 01.04.2017.

研究成果: ジャーナルへの寄稿記事

Yamauchi, Takayoshi ; Nishiyama, Masaaki ; Moroishi, Toshiro ; Kawamura, Atsuki ; Nakayama, Keiichi I. / FBXL5 inactivation in mouse brain induces aberrant proliferation of neural stem progenitor cells. :: Molecular and cellular biology. 2017 ; 巻 37, 番号 8.
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