Neurotrophins and Netrins Require Calcineurin/NFAT Signaling to Stimulate Outgrowth of Embryonic Axons
Open accessAbstract
Axon outgrowth is the first step in the formation of neuronal connections, but the pathways that regulate axon extension are still poorly understood. We find that mice deficient in calcineurin-NFAT signaling have dramatic defects in axonal outgrowth, yet have little or no defect in neuronal differentiation or survival. In vitro, sensory and commissural neurons lacking calcineurin function or NFATc2, c3, and c4 are unable to respond to neurotrophins or netrin-1 with efficient axonal outgrowth. Neurotrophins and netrins stimulate calcineurin-dependent nuclear localization of NFATc4 and activation of NFAT-mediated gene transcription in cultured primary neurons. These data indicate that the ability of these embryonic axons to respond to growth factors with rapid outgrowth requires activation of calcineurin/NFAT signaling by these factors. The precise parsing of signals for elongation turning and survival could allow independent control of these processes during development.
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Different neuronal cell types express different NFAT isoforms.
“However, recent studies have shown that neurons also express NFAT and that different neuronal cell types express different NFAT isoforms (67–70).”
From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [69]
Neurons also express NFAT.
“However, recent studies have shown that neurons also express NFAT and that different neuronal cell types express different NFAT isoforms (67–70).”
From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [69]
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- Authors
- Graef, I. A., Wang, F., Charron, F., Chen, L., Neilson, J., Tessier-Lavigne, M., & Crabtree, G. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Crabtree, Gerald R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 113
- Issue
- 5
- Pages
- 657-670
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2140884549
- Cited by
- 379
- References
- 3
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 11 · 2021: 11 · 2020: 13 · 2019: 9 · 2018: 17 · 2017: 12 · 2016: 21 · 2015: 20 · 2014: 22 · 2013: 17 · 2012: 13
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (PO1 DE 08973, CA 39612)
- Human Frontier Science Program
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- axon growth, calcineurin, NFAT signaling, neurotrophins, netrin-1, sensory neurons, commissural neurons, NFATc4, neuronal differentiation, neuronal survival, axon guidance, gene transcription
- MeSH terms
- Netrin-1, Animals, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Growth Substances, Mutation, Nerve Growth Factors, Nervous System, Nuclear Proteins, Protein Synthesis Inhibitors, Transcription Factors, Signal Transduction, Gene Expression Regulation, Developmental, Calcineurin, Growth Cones, Active Transport, Cell Nucleus, Tumor Suppressor Proteins, NFATC Transcription Factors, Mice, Calcineurin Inhibitors
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