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, Shinichi Sakakibara, Marc Tessier-Lavigne, Hirotaka James Okano, Hideyuki Okano

    Research output: Contribution to journalArticle

    50 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

    Fingerprint

    RNA-Binding Proteins
    Neurons
    Messenger RNA
    Cues
    Gene Expression
    Proteins
    Axon Guidance

    Keywords

    • Devbio
    • Molneuro
    • Signaling

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Neural RNA-Binding Protein Musashi1 Controls Midline Crossing of Precerebellar Neurons through Posttranscriptional Regulation of Robo3/Rig-1 Expression. / Kuwako, Ken ichiro; Kakumoto, Kyoko; Imai, Takao; Igarashi, Mana; Hamakubo, Takao; Sakakibara, Shinichi; Tessier-Lavigne, Marc; Okano, Hirotaka James; Okano, Hideyuki.

    In: Neuron, Vol. 67, No. 3, 08.2010, p. 407-421.

    Research output: Contribution to journalArticle

    Kuwako, Ken ichiro ; Kakumoto, Kyoko ; Imai, Takao ; Igarashi, Mana ; Hamakubo, Takao ; Sakakibara, Shinichi ; Tessier-Lavigne, Marc ; Okano, Hirotaka James ; Okano, Hideyuki. / Neural RNA-Binding Protein Musashi1 Controls Midline Crossing of Precerebellar Neurons through Posttranscriptional Regulation of Robo3/Rig-1 Expression. In: Neuron. 2010 ; Vol. 67, No. 3. pp. 407-421.
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