TNF-alpha contributes to the death of NGF-dependent neurons during development

Many sympathetic and sensory neurons depend on a supply of nerve growth factor (NGF) from their targets during development, and neurons that fail to obtain sufficient NGF die by apoptosis. Here we show that tumor necrosis factor alpha (TNF alpha) is involved in bringing about the death of NGF-deprived neurons. Function-blocking antibodies against either TNF alpha or TNF receptor 1 (TNFR1) rescued many sympathetic and sensory neurons following NGF deprivation in vitro. Fewer sympathetic and sensory neurons died during the phase of naturally occurring neuronal death in TNF-deficient embryos, and neurons from these embryos survived in culture better than wild-type neurons. These neurons coexpress TNF alpha and TNFR1 during this stage of development, suggesting that TNFa acts by an autocrine loop.