ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Netrin-1 induces axon branching in developing cortical neurons by frequency-dependent calcium signaling pathways.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 124 citations in OpenAlex.
- Adenylyl Cyclases as Therapeutic Targets in Neuroregeneration.International journal of molecular sciences · 2025Review
- Neuronal growth patterns and synapse formation are mediated by distinct activity-dependent mechanisms.Scientific reports · 2025Article
- Article
- In situ cryo-electron tomography reveals local cellular machineries for axon branch development.The Journal of cell biology · 2022Article
- Neuromodulatory control of inhibitory network arborization in the developing postnatal neocortex.Science advances · 2022Article
- Ryanodine Receptors: A Potential Treatment Target in Various Neurodegenerative Disease.Cellular and molecular neurobiology · 2021Review
- Local Translation Across Neural Development: A Focus on Radial Glial Cells, Axons, and Synaptogenesis.Frontiers in molecular neuroscience · 2021Review
- Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes.The Journal of biological chemistry · 2020Article
- Article
- Complement and T Cell Metabolism: Food for Thought.Immunometabolism · 2019Article
- Mapping Semaphorins and Netrins in the Pathogenesis of Human Thoracic Aortic Aneurysms.International journal of molecular sciences · 2019Article
- Macrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells.Nature communications · 2018Article
- Netrin-1/DCC-mediated PLCγ1 activation is required for axon guidance and brain structure development.EMBO reports · 2018Article
- MARCKS Is Necessary for Netrin-DCC Signaling and Corpus Callosum Formation.Molecular neurobiology · 2018Article
- Neuronal Ryanodine Receptors in Development and Aging.Molecular neurobiology · 2018Review
- Shift in the function of netrin-1 from axon outgrowth to axon branching in developing cerebral cortical neurons.BMC neuroscience · 2017Article
- It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches.Molecular and cellular neurosciences · 2017Review
- Article
- A novel role for the DNA repair gene Rad51 in Netrin-1 signalling.Scientific reports · 2017Article
- Keeping It All Going-Complement Meets Metabolism.Frontiers in immunology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
A single axon can innervate multiple targets by collateral branching. Axon branching is thus essential for establishing CNS connectivity. However, surprisingly little is known about the mechanisms by which branching is regulated. Axons often stop elongating before branches develop and anatomical and molecular data suggest that axon branching occurs independent of axon outgrowth. We found that netrin-1 dramatically increases cortical axon branching. Here, we sought to identify intracellular signaling components involved in netrin-1-induced axon branching. Using live cell imaging of dissociated developing cortical neurons, we show that netrin-1 rapidly increases the frequency of repetitive calcium transients. These transients are often restricted to small regions of the axon. Simultaneous imaging of calcium activity and development of axon branches revealed that Ca2+ transients coincide spatially and temporally with protrusion of branches from the axon. Remarkably, fully formed branches with motile growth cones could develop de novo within 20 min. Netrin-1-induced Ca2+ transients involve release from intracellular stores and Ca2+ signaling is essential for netrin-1-induced axon branching. Using techniques to overexpress or suppress kinase activity, we find that calcium/calmodulin-dependent protein kinase II (CaMKII) and mitogen-activated protein kinase (MAPK) are major downstream targets of the netrin-1 calcium signaling pathway and are required for axon branching. CaMKII, but not MAPK, is also involved in axon outgrowth. The role of CaMKII and MAPKs in axon branching is consistent with the sensitivity of these kinases to changes in the frequency Ca2+ transients. Together, these novel findings define calcium signaling mechanisms required for development of new axon branches promoted by a guidance cue.
Indexed as
Identifiers
What OpenQuestion holds
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.