Fas/tumor necrosis factor receptor death signaling is required for axotomy-induced death of motoneurons in vivo.
Activation of the Fas death receptor leads to the death of motoneurons in culture. To investigate the role of Fas in programmed cell death and pathological situations, we used several mutant mice deficient for Fas signaling and made a novel transgenic FADD-DN (FAS-associated death domain-dominant-negative) strain. In vitro, motoneurons from all of these mice were found to be resistant to Fas activation and to show a delay in trophic deprivation-induced death. During normal development in vivo, no changes in motoneuron survival were observed. However, the number of surviving motoneurons was twofold higher in animals deficient for Fas signaling after facial nerve transection in neonatal mice. These results reveal a novel role for Fas as a trigger of axotomy-induced death and suggest that the Fas pathway may be activated in pathological degeneration of motoneurons.
D000199:Actins / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019771:Axotomy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005154:Facial Nerve / Q000502:physiology; D053200:Fas-Associated Death Domain Protein; D005799:Genes, Dominant; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor