Neural RNA-Binding Protein Musashi1 Controls Midline Crossing of Precerebellar Neurons through Posttranscriptional Regulation of Robo3/Rig-1 Expression

Ken ichiro Kuwako*, Kyoko Kakumoto, Takao Imai, Mana Igarashi, Takao Hamakubo, Shin ichi Sakakibara, Marc Tessier-Lavigne, Hirotaka James Okano, Hideyuki Okano

*この研究の対応する著者

研究成果: Article査読

57 被引用数 (Scopus)

抄録

Precisely regulated spatiotemporal gene expression is essential for the establishment of neural circuits. In contrast to the increasing evidence for transcriptional regulation of axon guidance cues and receptors, the role of posttranscriptional regulation in axon guidance, especially in vivo, remains poorly characterized. Here, we demonstrate that the expression of Slit receptor Robo3/Rig-1, which plays crucial roles in axonal midline crossing, is regulated by a neural RNA-binding protein Musashi1 (Msi1). Msi1 binds to Robo3 mRNA through RNA recognition motifs and increases the protein level of Robo3 without affecting its mRNA level. In Msi1-deficient precerebellar neurons, Robo3 protein, but not its mRNA, is dramatically reduced. Moreover, similar to defects in Robo3-deficient mice, axonal midline crossing and neuronal migration of precerebellar neurons are severely impaired in Msi1-deficient mice. Together, these findings indicate that Msi1-mediated posttranscriptional regulation of Robo3 controls midline crossing of precerebellar neurons.

本文言語English
ページ(範囲)407-421
ページ数15
ジャーナルNeuron
67
3
DOI
出版ステータスPublished - 2010 8

ASJC Scopus subject areas

  • 神経科学(全般)

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