NGF-promoted axon growth and target innervation requires GITRL-GITR signaling
- 6 January 2008
- journal article
- research article
- Published by Springer Nature in Nature Neuroscience
- Vol. 11 (2) , 135-142
- https://doi.org/10.1038/nn2034
Abstract
Nerve growth factor (NGF) has an important role in regulating sympathetic neuron survival and target field innervation during development. Here we show that glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR), a member of the TNF superfamily, and its ligand (GITRL) are co-expressed in mouse sympathetic neurons when their axons are innervating their targets under the influence of target-derived NGF. In culture, GITRL enhanced NGF-promoted neurite growth from neonatal sympathetic neurons, and preventing GITR-GITRL interaction in these neurons or knocking down GITR inhibited NGF-promoted neurite growth without affecting neuronal survival. Tnfrsf18−/− (Gitr) neonates have reduced sympathetic innervation density in vivo compared with Gitr+/+ littermates. GITR activation is required for the phosphorylation of extracellular signal–regulated kinases 1 and 2 by NGF that is necessary for neurite growth. Our results reveal a previously unknown signaling loop in developing sympathetic neurons that is crucial for NGF-dependent axon growth and target innervation.Keywords
This publication has 31 references indexed in Scilit:
- A Neurotrophin Signaling Cascade Coordinates Sympathetic Neuron Development through Differential Control of TrkA Trafficking and Retrograde SignalingPublished by Elsevier ,2004
- Frontline: GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulationsEuropean Journal of Immunology, 2004
- Heterogeneous Requirement of NGF for Sympathetic Target InnervationIn VivoJournal of Neuroscience, 2004
- MEK/ERK pathway is aberrantly active in Hodgkin disease: a signaling pathway shared by CD30, CD40, and RANK that regulates cell proliferation and survivalBlood, 2003
- NEW EMBO MEMBER'S REVIEW: Regulation of neuronal survival and death by extracellular signals during developmentThe EMBO Journal, 2003
- Macrophage stimulating protein is a target-derived neurotrophic factor for developing sensory and sympathetic neuronsDevelopment, 2003
- Role of GITR in activation response of T lymphocytesBlood, 2002
- TNFα contributes to the death of NGF-dependent neurons during developmentNature Neuroscience, 2001
- The TrkB-Shc Site Signals Neuronal Survival and Local Axon Growth via MEK and PI3-KinaseNeuron, 2000
- Developmental neuron death in the rat superior cervical sympathetic ganglion: cell counts and ultrastructureJournal of Neurocytology, 1983