Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Human Disease Variation in the Light of Population Genomics

    Research output: Contribution to journalReviewResearchpeer-review

  4. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Myelodysplastic syndrome patient-derived xenografts: from no options to many

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations
Growth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs). However, the mechanisms that regulate local translation are poorly understood. Here we show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3.2 expression. These data show that local translation is regulated by mRNA stability and that NMD acts locally to influence axonal pathfinding.
Original languageEnglish
JournalCell
Volume153
Issue number6
Pages (from-to)1252-65
Number of pages14
ISSN0092-8674
DOIs
Publication statusPublished - 6 Jun 2013

    Research areas

  • Animals, Axons, Embryo, Mammalian, Growth Cones, Membrane Proteins, Mice, Nerve Tissue Proteins, Neurons, Nonsense Mediated mRNA Decay, Protein Biosynthesis, RNA Isoforms, RNA Stability, Spinal Cord

ID: 40038196