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

O'Keeffe, Gerard W., Gutierrez, Humberto, Pandolfi, Pier Paolo , Riccardi, Carlo and Davies, Alun M. (2008) NGF-promoted axon growth and target innervation requires GITRL-GITR signaling. Nature Neuroscience, 11 (2). pp. 135-42. ISSN 1097-6256

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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.

Keywords:Neuronal Development
Subjects:C Biological Sciences > C141 Developmental Biology
Divisions:College of Science > School of Life Sciences
ID Code:7859
Deposited On:21 Mar 2013 11:17

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