ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
A TrkB/EphrinA interaction controls retinal axon branching and synaptogenesis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 162 citations in OpenAlex.
- The Eph-ephrin system in neuropsychiatric and neurodevelopmental disorders.Journal of psychiatry & neuroscience : JPN · 2026Review
- Functional and evolutionary characteristics of human genes encoding cell surface receptors involved in the regulation of appetite.Journal of integrative bioinformatics · 2025Article
- EphA2 and Ephrin-A1 Utilize the Same Interface for BothbioRxiv : the preprint server for biology · 2025Article
- Calcitriol Modulates Hippocampal Axon Guidance Through Enhanced EfnA4-Mediated PI3K/AKT Signaling in an Autism Mouse Model.CNS neuroscience & therapeutics · 2025Article
- Neuritin: a multifaceted neuroprotective factor with emerging applications for neurodegeneration.Frontiers in neuroscience · 2025Review
- Article
- Antagonistic Activities of Fmn2 and ADF Regulate Axonal F-Actin Patch Dynamics and the Initiation of Collateral Branching.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Hedgehog signaling activates a mammalian heterochronic gene regulatory network controlling differentiation timing across lineages.Developmental cell · 2022Article
- Article
- Roles of Eph-Ephrin Signaling in the Eye Lens Cataractogenesis, Biomechanics, and Homeostasis.Frontiers in cell and developmental biology · 2022Review
- Article
- Genetic interplay between transcription factor Pou4f1/Brn3a and neurotrophin receptor Ret in retinal ganglion cell type specification.Neural development · 2021Article
- Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison?Biomolecules · 2021Review
- Local Translation Across Neural Development: A Focus on Radial Glial Cells, Axons, and Synaptogenesis.Frontiers in molecular neuroscience · 2021Review
- The GTPase Arl8B Plays a Principle Role in the Positioning of Interstitial Axon Branches by Spatially Controlling Autophagosome and Lysosome Location.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Molecular complexity of visual mapping: a challenge for regenerating therapy.Neural regeneration research · 2020Review
- Neurogenesis From Neural Crest Cells: Molecular Mechanisms in the Formation of Cranial Nerves and Ganglia.Frontiers in cell and developmental biology · 2020Review
- FIGNL1 associates with KIF1Bβ and BICD1 to restrict dynein transport velocity during axon navigation.The Journal of cell biology · 2019Article
- The RTK Interactome: Overview and Perspective on RTK Heterointeractions.Chemical reviews · 2019Review
- RasGRF1 mediates brain-derived neurotrophic factor-induced axonal growth in primary cultured cortical neurons.Biochemistry and biophysics reports · 2019Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Toward understanding topographically specific branching of retinal axons in their target area, we have studied the interaction between neurotrophin receptors and members of the Eph family. TrkB and its ligand BDNF are uniformly expressed in the retina and tectum, respectively, and exert a branch-promoting activity, whereas EphAs and ephrinAs are expressed in gradients in retina and tectum and can mediate a suppression of axonal branching. We have identified a novel cis interaction between ephrinA5 and TrkB on retinal ganglion cell axons. TrkB interacts with ephrinA5 via its second cysteine-rich domain (CC2), which is necessary and sufficient for binding to ephrinA5. Their functional interaction is twofold: ephrinA5 augments BDNF-promoted retinal axon branching in the absence of its activator EphA7-Fc, whereas EphA7-Fc application abolishes branching in a local and concentration-dependent manner. The importance of TrkB in this process is shown by the fact that overexpression of an isolated TrkB-CC2 domain interfering with the ephrinA/TrkB interaction abolishes this regulatory interplay, whereas knockdown of TrkB via RNA interference diminishes the ephrinA5-evoked increase in branching. The ephrinA/Trk interaction is neurotrophin induced and specifically augments the PI-3 kinase/Akt pathway generally known to be involved in the promotion of branching. In addition, ephrinAs/TrkB modulate axon branching and also synapse formation of hippocampal neurons. Our findings uncover molecular mechanisms of how spatially restricted axon branching can be achieved by linking globally expressed branch-promoting with differentially expressed branch-suppressing activities. In addition, our data suggest that growth factors and the EphA-ephrinA system interact in a way that affects axon branching and synapse development.
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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.