ArticleThe Journal of biological chemistry2013
c-Jun N-terminal kinase 1 (JNK1) is required for coordination of netrin signaling in axon guidance.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- c-Jun in neurodegeneration: A key transcriptional regulator with therapeutic implications.Molecular therapy. Nucleic acids · 2026Review
- Future Directions for Studying the Potential of Mammalian Dscam in Autism Spectrum Disorder and Alzheimer's Disease: Insights from Dose Sensitivity.Molecular neurobiology · 2025Review
- Exploring perspectives of Dscam for cognitive deficits: a review of multifunction for regulating neural wiring in homeostasis.Frontiers in molecular neuroscience · 2025Review
- miR-193b-365 microcluster downstream ofiScience · 2024Article
- Netrin-1 as A neural guidance protein in development and reinnervation of the larynx.Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft · 2024Review
- The role of microtubule-associated protein tau in netrin-1 attractive signaling.Journal of cell science · 2024Article
- In toto imaging of glial JNK signaling during larval zebrafish spinal cord regeneration.Development (Cambridge, England) · 2023Article
- Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling.Neural regeneration research · 2023Article
- Radiolabeled Aminopyrazoles as Novel Isoform Selective Probes for pJNK3 Quantification.ACS medicinal chemistry letters · 2022Article
- Role of DSCAM in the Development of Neural Control of Movement and Locomotion.International journal of molecular sciences · 2021Review
- Phosphorylation of GAP-43 T172 is a molecular marker of growing axons in a wide range of mammals including primates.Molecular brain · 2021Article
- c-Jun N-terminal kinase 1 (JNK1) modulates oligodendrocyte progenitor cell architecture, proliferation and myelination.Scientific reports · 2021Article
- Review
- Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling.Nature cell biology · 2020Article
- Neuronal Signaling Involved in Neuronal Polarization and Growth: Lipid Rafts and Phosphorylation.Frontiers in molecular neuroscience · 2020Article
- Review
- Molecular basis of the functions of the mammalian neuronal growth cone revealed using new methods.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2019Review
- A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways.Neural plasticity · 2019Review
- Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death.Cell death & disease · 2018Article
- miR-92 Suppresses Robo1 Translation to Modulate Slit Sensitivity in Commissural Axon Guidance.Cell reports · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The JNK family of MAPKs is involved in a large variety of physiological and pathological processes in brain development, such as neural survival, migration, and polarity as well as axon regeneration. However, whether JNK activation is involved in axon guidance remains unknown. Here, we provide evidence indicating the JNK pathway is required for Netrin signaling in the developing nervous system. Netrin-1 increased JNK1, not JNK2 or JNK3, activity in the presence of deleted in colorectal cancer (DCC) or Down syndrome cell adhesion molecule (DSCAM), and expression of both of them further enhanced Netrin-1-induced JNK1 activity in vitro. Inhibition of JNK signaling either by a JNK inhibitor, SP600125, or expression of a dominant negative form of MKK4, a JNK upstream activator, blocked Netrin-1-induced JNK1 activation in HEK293 cells. Netrin-1 increased endogenous JNK activity in primary neurons. Netrin-1-induced JNK activation was inhibited either by the JNK inhibitor or an anti-DCC function-blocking antibody. Combination of the anti-DCC function-blocking antibody with expression of DSCAM shRNA in primary neurons totally abolished Netrin-1-induced JNK activation, whereas knockdown of DSCAM partially inhibited the Netrin-1 effect. In the developing spinal cord, phospho-JNK was strongly expressed in commissural axons before and as they crossed the floor plate, and Netrin-1 stimulation dramatically increased the level of endogenous phospho-JNK in commissural axon growth cones. Inhibition of JNK signaling either by JNK1 RNA interference (RNAi) or the JNK inhibitor suppressed Netrin-1-induced neurite outgrowth and axon attraction. Knockdown of JNK1 in ovo caused defects in spinal cord commissural axon projection and pathfinding. Our study reveals that JNK1 is important in the coordination of DCC and DSCAM in Netrin-mediated attractive signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.