Neural RNA-binding protein Musashi1 controls midline crossing of precerebellar neurons through posttranscriptional regulation of Robo3/Rig-1 expression.
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.
Kuwako
Ken-ichiro
K
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. kuwako@sc.itc.keio.ac.jp
Kakumoto
Kyoko
K
Imai
Takao
T
Igarashi
Mana
M
Hamakubo
Takao
T
Sakakibara
Shin-ichi
S
Tessier-Lavigne
Marc
M
Okano
Hirotaka James
HJ
Okano
Hideyuki
H
D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002465:Cell Movement / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development / Q000502:physiology; D002522:Chlorocebus aethiops; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000502:physiology*; D011956:Receptors, Cell Surface; D012249:Rhombencephalon / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D000097905:Roundabout Proteins
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; C104786:Msi1h protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins