Gene activation is required for developmentally programmed cell death.

Abstract

The intersegmental muscles of the tobacco hawkmoth Manduca sexta die during the 36-hr period after metamorphosis. The trigger for cell death is a fall in the ecdysteroid titer. Commitment of the intersegmental muscles to degenerate involves selective repression and activation of ecdysteroid-responsive genes. When the pattern of gene expression is altered after injection of either 20-hydroxyecdysone or actinomycin D, the muscles persist. cDNA clones have been isolated for four genes that become abundantly expressed coincident with the commitment to degenerate. The data presented here indicate that programmed cell death is not due to the cessation of macromolecular synthesis in condemned cells but rather is due to the activation of a differentiative pathway.During both embryonic and post-embryonic development, many cells die by a process that appears to be independent of age-related senescence (1). This developmentally programmed cell death serves a variety of functions in different systems. For example, much of the sculpting of the body form involves the removal of unneeded cells, such as in the formation of the digits during embryogenesis (2). Cell death can also serve to adjust the number of neurons innervating either central or peripheral targets (3). As well, cell death can remove obsolete tissues during development, as occurs during metamorphosis in amphibia (4) and insects (5, 6).Despite the ubiquity of programmed cell death, there is relatively little information available regarding either the triggers or mechanisms that mediate this process. In the embryonic chicken nervous system, motor neuron degeneration appears to be regulated by competition among neurons for peripheral muscle targets (3). A muscle-derived "trophic" factor is currently being purified for characterization (7). In the nematode Caenorhabditis elegans, the trigger(s) responsible for programmed cell death are unknown, although several mutations have been identified that block normal patterns of neuron loss (8, 9). The molecular isolation and characterization of the genes containing these mutations may provide considerable insight into the mechanisms of cell death.Another system that has proven useful for the analysis of cell death is the intersegmental muscles (ISMs) of Lepidoptera (10). Each fiber within these muscles is approximately 5 mm long and 1 mm in diameter. The fibers are organized in sheets that span each of the abdominal segments in the larva. After pupation, the ISMs in the first two and last two segments degenerate, leaving four segments of intact muscle remaining. The ISMs are then retained until 3 days before adult eclosion (day 15 of development) at which point they begin to atrophy. Atrophy results in a loss of 40% of muscle mass, without any change in resting potential, force/ cross sectional area, or skinned-fiber calcium sensitivity (L.M.S., unpublished data). The ISMs are used during the performance of the eclosion (emergence) behavior on day 18, the last day of pupal/adult development. After eclosion, the ISM...

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Programmed cell death in flight muscle histolysis of the house cricket

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