Genetic analysis in the nematode C. elegans revealed that two genes, ced-3
and ced-4, are absolutely required for all developmentally regulated cell
deaths.3 The product of the ced-4 gene shares some similarity to Apaf-1, the
docking protein that appears to be involved in caspase activation in mammalian
cells.10,60 The product of the ced-3 gene has significant structural11 and
functional 12,134 homology to mammalian caspases. Interestingly, the supernumerary
cells that survive when these genes are disrupted are typically neurons,3
indicating that products of these genes participate in neuronal apoptosis. Conversely,
the demonstration that mice lacking caspase-3 or -9 have central nervous
system abnormalities as a consequence of diminished developmentally
regulated neuronal apoptosis135, 135a suggests that these caspases play unique
roles in neuronal PCD in the developing mammalian central nervous system.