O'Keeffe, Gerard, Gutierrez, Humberto ![]() ![]() |
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.
Item Type: | Article |
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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 |
URI: | https://orca.cardiff.ac.uk/id/eprint/22262 |
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