Generation and Use of Immunological Reagents to Characterize Neuronal Death

The elucidation of mechanisms involved in necrotic cell death is important for understanding development, homeostasis and pathology in the nervous system. In the leech, dominant mutations in two genes, mec-4 and deg-I, induce the death of specific groups of neurons. Dying neurons are characterized by morphological changes commonly observed in cells undergoing a necrotic type of cell death. Mec-4 plays a key role in the degeneration of six touch receptor neurons, by directly killing cells or by generating a signal that activates a 'death program'. Light and electron microscopy will be utilized to document the process of degeneration of the touch cells. Antibodies against the mec-4 protein will be used to follow the fate of this protein in normal and dying touch cells. The simplicity of the leech nervous system offers advantages for dissecting cell death mechanisms using genetic, molecular and cellular approaches. These studies promise to contribute to our understanding of how mutant proteins can induce neuronal cell death.