NGF-promoted axon growth and target innervation requires GITRL-GITR signaling (Nat Neurosci, 2008, 11:135-142)

報告日期: 2008/05/16
報告時間: 15:10/16:00
報告學生: 童志偉
講評老師: 張 玲

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

Nature Neuroscience 11(2):135-142, 2008

Speaker: Tong, Chih-Wei

Commentator: Chang, Christina Ling, Ph.D.


Axon growth and target innervation are common and critical phenomena during development of nerve system. Nerve growth factor (NGF), an attractive guidance molecule, is necessary for the innervation and survival of sympathetic neurons. However, the mechanisms are not clear. Sympathetic neurons of the developing superior cervical ganglion (SCG) are an extensive model for analyzing the mechanism of neuronal development. The authors found that transcripts of glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) were highly expressed in the developing SCG by PCR screen. GITR and its ligand, GITRL were co-expressed in the neurons of SCG. The expression level of GGITR increased at E15, peaked at P1, and declined at P5. Authors further used overexpression of GITR and antisense GITR RNA to demonstrate the involvement of GITRL-GITR signaling in NGF-promoted axon growth. Gitr(-/-) mice showed that GITRL-GITR signaling facilitated NGF-promoted axon growth and neuron innervation, but not survival. Moreover, it influenced axon growth over a developmental window. Using a MAP kinase inhibitor, U1025, authors also found that ERK1/2 activation was involved in GITR-enhanced axonal growth in GITR KO mice. This study reveals that GITR signaling plays a co-stimulatory role in NGF-dependent axonal growth, branching and target innervation.



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