論文

査読有り
2014年4月

Specification of Spatial Identities of Cerebellar Neuron Progenitors by Ptf1a and Atoh1 for Proper Production of GABAergic and Glutamatergic Neurons

JOURNAL OF NEUROSCIENCE
  • Mayumi Yamada
  • ,
  • Yusuke Seto
  • ,
  • Shinichiro Taya
  • ,
  • Tomoo Owa
  • ,
  • Yukiko U. Inoue
  • ,
  • Takayoshi Inoue
  • ,
  • Yoshiya Kawaguchi
  • ,
  • Yo-ichi Nabeshima
  • ,
  • Mikio Hoshino

34
14
開始ページ
4786
終了ページ
4800
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1523/JNEUROSCI.2722-13.2014
出版者・発行元
SOC NEUROSCIENCE

In the cerebellum, the bHLH transcription factors Ptf1a and Atoh1 are expressed in distinct neuroepithelial regions, the ventricular zone (VZ) and the rhombic lip (RL), and are required for producing GABAergic and glutamatergic neurons, respectively. However, it is unclear whether Ptf1a or Atoh1 is sufficient for specifying GABAergic or glutamatergic neuronal fates. To test this, we generated two novel knock-in mouse lines, Ptf1a(Atoh1) and Atoh1(Ptf1a), that are designed to express Atoh1 and Ptf1a ectopically in the VZ and RL, respectively. In Ptf1a(Atoh1) embryos, ectopically Atoh1-expressing VZ cells produced glutamatergic neurons, including granule cells and deep cerebellar nuclei neurons. Correspondingly, in Atoh1(Ptf1a) animals, ectopically Ptf1a-expressing RL cells produced GABAergic populations, such as Purkinje cells and GABAergic interneurons. Consistent results were also obtained from in utero electroporation of Ptf1a or Atoh1 into embryonic cerebella, suggesting that Ptf1a and Atoh1 are essential and sufficient for GABAergic versus glutamatergic specification in the neuroepithelium. Furthermore, birthdating analyses with BrdU in the knock-in mice or with electroporation studies showed that ectopically produced fate-changed neuronal types were generated at temporal schedules closely simulating those of the wild-type RL and VZ, suggesting that the VZ and RL share common temporal information. Observations of knock-in brains as well as electroporated brains revealed that Ptf1a and Atoh1 mutually negatively regulate their expression, probably contributing to formation of non-overlapping neuroepithelial domains. These findings suggest that Ptf1a and Atoh1 specify spatial identities of cerebellar neuron progenitors in the neuroepithelium, leading to appropriate production of GABAergic and glutamatergic neurons, respectively.

Web of Science ® 被引用回数 : 57

リンク情報
DOI
https://doi.org/10.1523/JNEUROSCI.2722-13.2014
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000334076000005&DestApp=WOS_CPL
ID情報
  • DOI : 10.1523/JNEUROSCI.2722-13.2014
  • ISSN : 0270-6474
  • Web of Science ID : WOS:000334076000005

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