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NGF-promoted axon growth and target innervation requires GITRL-GITR signaling

O'Keeffe, Gerard, Gutierrez, Humberto ORCID:, Pandolfi, Pier Paolo, Riccardi, Carlo and Davies, Alun M. ORCID: 2008. NGF-promoted axon growth and target innervation requires GITRL-GITR signaling. Nature Neuroscience 11 (2) , pp. 135-142. 10.1038/nn2034

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Nature Publishing Group
ISSN: 1097-6256
Last Modified: 19 Oct 2022 09:48

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