STEROID REGULATED PROGRAMMED CELL-DEATH DURING DROSOPHILA-METAMORPHOSIS

During insect metamorphosis, pulses of the steroid hormone 20-hydroxye cdysone (ecdysone) direct the destruction of obsolete larval tissues a nd their replacement by tissues and structures that form the adult hy. We show here that larval midgut and salivary gland histolysis are sta ge-specific steroid-triggered programmed cell death responses, Dying l arval midgut and salivary gland cell nuclei become permeable to the vi tal dye acridine orange and their DNA undergoes fragmentation, indicat ive of apoptosis, Furthermore, the histolysis of these tissues can be inhibited by ectopic expression of the baculovirus anti-apoptotic prot ein p35, implicating a role for caspases in the death response. Coordi nate stage-specific induction of the Drosophila death genes reaper (Ip l) and head involution defective (hid) immediately precedes the destru ction of the larval midgut and salivary gland, In addition, the diap2 anti-cell death gene is repressed in larval salivary glands as rpr and hid are induced, suggesting that the death of this tissue is under bo th positive and negative regulation, Finally, diap2 is repressed by ec dysone in cultured salivary glands under the same conditions that indu ce rpr expression and trigger programmed cell death. These studies ind icate that ecdysone directs the death of larval tissues via the precis e stage-and tissue-specific regulation of key death effector genes.