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Drosophila caspases involved in developmentally regulated programmed cell death of peptidergic neurons during early metamorphosis
Author(s) -
Lee Gyunghee,
Wang Zixing,
Sehgal Ritika,
Chen ChunHong,
Kikuno Keiko,
Hay Bruce,
Park Jae H.
Publication year - 2010
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22498
Subject(s) - biology , caspase , programmed cell death , effector , microbiology and biotechnology , apoptosis , mutation , gene , genetics
A great number of obsolete larval neurons in the Drosophila central nervous system are eliminated by developmentally programmed cell death (PCD) during early metamorphosis. To elucidate the mechanisms of neuronal PCD occurring during this period, we undertook genetic dissection of seven currently known Drosophila caspases in the PCD of a group of interneurons (vCrz) that produce corazonin (Crz) neuropeptide in the ventral nerve cord. The molecular death program in the vCrz neurons initiates within 1 hour after pupariation, as demonstrated by the cytological signs of cell death and caspase activation. PCD was significantly suppressed in dronc ‐null mutants, but not in null mutants of either dredd or strica . A double mutation lacking both dronc and strica impaired PCD phenotype more severely than did a dronc mutation alone, but comparably to a triple dredd/strica/dronc mutation, indicating that dronc is a main initiator caspase, while strica plays a minor role that overlaps with dronc 's. As for effector caspases, vCrz PCD requires both ice and dcp‐1 functions, as they work cooperatively for a timely removal of the vCrz neurons. Interestingly, the activation of the Ice and Dcp‐1 is not solely dependent on Dronc and Strica, implying an alternative pathway to activate the effectors. Two remaining effector caspase genes, decay and damm , found no apparent functions in the neuronal PCD, at least during early metamorphosis. Overall, our work revealed that vCrz PCD utilizes dronc, strica, dcp‐1 , and ice wherein the activation of Ice and Dcp‐1 requires a novel pathway in addition to the initiator caspases. J. Comp. Neurol. 519:34‐48, 2011. © 2010 Wiley‐Liss, Inc.