論文

査読有り 国際誌
2019年7月31日

FGF Signaling Directs the Cell Fate Switch from Neurons to Astrocytes in the Developing Mouse Cerebral Cortex.

The Journal of neuroscience : the official journal of the Society for Neuroscience
  • Tung Anh Dinh Duong
  • ,
  • Yoshio Hoshiba
  • ,
  • Kengo Saito
  • ,
  • Kanji Kawasaki
  • ,
  • Yoshie Ichikawa
  • ,
  • Naoyuki Matsumoto
  • ,
  • Yohei Shinmyo
  • ,
  • Hiroshi Kawasaki

39
31
開始ページ
6081
終了ページ
6094
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1523/JNEUROSCI.2195-18.2019

During mammalian neocortical development, neural precursor cells generate neurons first and astrocytes later. The cell fate switch from neurons to astrocytes is a key process generating proper numbers of neurons and astrocytes. Although the intracellular mechanisms regulating this cell fate switch have been well characterized, extracellular regulators are still largely unknown. Here, we uncovered that fibroblast growth factor (FGF) regulates the cell fate switch from neurons to astrocytes in the developing cerebral cortex using mice of both sexes. We found that the FGF signaling pathway is activated in radial glial cells of the ventricular zone at time points corresponding to the switch in cell fate. Our loss- and gain-of-function studies using in utero electroporation indicate that activation of FGF signaling is necessary and sufficient to change cell fates from neurons to astrocytes. We further found that the FGF-induced neuron-astrocyte cell fate switch is mediated by the MAPK pathway. These results indicate that FGF is a critical extracellular regulator of the cell fate switch from neurons to astrocytes in the mammalian cerebral cortex.SIGNIFICANCE STATEMENT Although the intracellular mechanisms regulating the neuron-astrocyte cell fate switch in the mammalian cerebral cortex during development have been well studied, their upstream extracellular regulators remain unknown. By using in utero electroporation, our study provides in vivo data showing that activation of FGF signaling is necessary and sufficient for changing cell fates from neurons to astrocytes. Manipulation of FGF signaling activity led to drastic changes in the numbers of neurons and astrocytes. These results indicate that FGF is a key extracellular regulator determining the numbers of neurons and astrocytes in the mammalian cerebral cortex, and is indispensable for the establishment of appropriate neural circuitry.

リンク情報
DOI
https://doi.org/10.1523/JNEUROSCI.2195-18.2019
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31175212
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668205
ID情報
  • DOI : 10.1523/JNEUROSCI.2195-18.2019
  • PubMed ID : 31175212
  • PubMed Central 記事ID : PMC6668205

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