| First Author | O'Keeffe GW | Year | 2008 |
| Journal | Nat Neurosci | Volume | 11 |
| Issue | 2 | Pages | 135-42 |
| PubMed ID | 18176559 | Mgi Jnum | J:131017 |
| Mgi Id | MGI:3772710 | Doi | 10.1038/nn2034 |
| Citation | O'Keeffe GW, et al. (2008) NGF-promoted axon growth and target innervation requires GITRL-GITR signaling. Nat Neurosci 11(2):135-42 |
| abstractText | 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. |
