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

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)407-421
Number of pages15
JournalNeuron
Volume67
Issue number3
DOIs
Publication statusPublished - 2010 Aug 1

Keywords

  • Devbio
  • Molneuro
  • Signaling

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kuwako, K. I., Kakumoto, K., Imai, T., Igarashi, M., Hamakubo, T., Sakakibara, S. I., Tessier-Lavigne, M., Okano, H. J., & Okano, H. (2010). Neural RNA-Binding Protein Musashi1 Controls Midline Crossing of Precerebellar Neurons through Posttranscriptional Regulation of Robo3/Rig-1 Expression. Neuron, 67(3), 407-421. https://doi.org/10.1016/j.neuron.2010.07.005