Induction of cell death by endogenous nerve growth factor through its p75 receptor

During development, neuronal survival is regulated by the limited availability of neurotrophins, which are proteins of the nerve growth factor (NGF) family. Activation of specific trk tyrosine kinase receptors by the neurotrophins blocks programmed cell death. The trkA-specific ligand NGF has also been shown to activate the non-tyrosine kinase receptor p75, a member of the tumour necrosis factor (TNF) receptor and Fas (APO-1/CD95) family. Here we report that, early in development, endogenous NGF causes the death of retinal neurons that express p75 but not trkA. These results indicate that, as with cells of the immune system, the death of neurons in the central nervous system can also be induced by ligands, and that the effect of NGF on cell fate depends on the type of receptor expressed by developing neurons.