Npgrj_NN_2034 135..142
نویسندگان
چکیده
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. Tnfrsf182/2 (Gitr) neonates have reduced sympathetic innervation density in vivo compared with Gitr1/1 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.
منابع مشابه
Sports Med 2006; 36 (2): 133-149
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 1. Rationale for the Existence of a Neural Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 2. Evidence for Neural Enhancement . . . . . . . . . . . . . . . . . . . . . . . . . ....
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