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

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