The p75 nerve growth factor receptor mediates survival or death depending on the stage of sensory neuron development.
The function of the low-affinity nerve growth factor (NGF) receptor, p75NGFR, in regulating neuronal survival during development is unclear. The sensory deficit in mice with mutated p75NGFR suggests it is necessary for development of sensory neurons; however, whether it is required, in addition to trkA, for signal transduction or is more involved in localization of NGF is unresolved. In this study we demonstrate, in vitro, that lowering the levels of p75NGFR expression in sensory neurons with antisense oligonucleotides largely prevents the NGF-mediated survival of sensory neurons from embryonic day 12 and 15 mice but increases the survival of embryonic day 19 and postnatal day 2 sensory neurons in the absence of NGF. Thus, the p75NGFR is required for NGF-mediated survival in neurons at the stage of target innervation but can mediate an apoptotic signal at a later stage of cell development. Thus, p75NGFR undergoes a switch in function in the perinatal period: during embryogenesis it is required, probably with trkA, to mediate neuronal survival in the presence of NGF, but in the early postnatal period it acts as a constitutive death signal in the absence of NGF.
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
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GL
Barrett
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Bartlett
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D002645:Chickens; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D013462:Sulfur Radioisotopes; D013873:Thionucleotides
D009414:Nerve Growth Factors; D016376:Oligonucleotides, Antisense; D017475:Receptors, Nerve Growth Factor; D013462:Sulfur Radioisotopes; D013873:Thionucleotides