Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations in Drosophila

被引:279
作者
Pérez-Garijo, A [1 ]
Martín, FA [1 ]
Morata, G [1 ]
机构
[1] Univ Autonoma Madrid, Ctr Biol Mol, CSIC, E-28049 Madrid, Spain
来源
DEVELOPMENT | 2004年 / 131卷 / 22期
关键词
Drosophila; apoptosis; caspase activity; wing disc; wg dpp;
D O I
10.1242/dev.01432
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Programmed cell death or apoptosis plays an important role in the development of multicellular organisms and can also be induced by various stress events. In the Drosophila wing imaginal disc there is little apoptosis in normal development but X-rays can induce high apoptotic levels, which eliminate a large fraction of the disc cells. Nevertheless, irradiated discs form adult patterns of normal size, indicating the existence of compensatory mechanisms. We have characterised the apoptotic response of the wing disc to X-rays and heat shock and also the developmental consequences of compromising apoptosis. We have used the caspase inhibitor P35 to prevent the death of apoptotic cells and found that it causes increased non-autonomous cell proliferation, invasion of compartments and persistent misexpression of the wingless (wg) and decapentaplegic (dpp) signalling genes. We propose that a feature of cells undergoing apoptosis is to activate wg and dpp, probably as part of the mechanism to compensate for cell loss. If apoptotic cells are not eliminated, they continuously emit Wg and Dpp signals, which results in developmental aberrations. We suggest that a similar process of uncoupling apoptosis initiation and cell death may occur during tumour formation in mammalian cells.
引用
收藏
页码:5591 / 5598
页数:8
相关论文
共 41 条
[1]   Regulators of IAP function: coming to grips with the grim reaper [J].
Bergmann, A ;
Yang, AYP ;
Srivastava, M .
CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (06) :717-724
[2]   Linking colorectal cancer to Wnt signaling [J].
Bienz, M ;
Clevers, H .
CELL, 2000, 103 (02) :311-320
[3]  
BLACK JL, 1991, MANIPULATING PIG PRO, V3, P111
[4]  
BRAND AH, 1993, DEVELOPMENT, V118, P401
[5]   Drosophila p53 binds a damage response element at the reaper locus [J].
Brodsky, MH ;
Nordstrom, W ;
Tsang, G ;
Kwan, E ;
Rubin, GM ;
Abrams, JM .
CELL, 2000, 101 (01) :103-113
[7]  
Burke R, 1996, DEVELOPMENT, V122, P2261
[8]   Visualization of gene expression in living adult Drosophila [J].
Calleja, M ;
Moreno, E ;
Pelaz, S ;
Morata, G .
SCIENCE, 1996, 274 (5285) :252-255
[9]   grim, a novel cell death gene in Drosophila [J].
Chen, P ;
Nordstrom, W ;
Gish, B ;
Abrams, JM .
GENES & DEVELOPMENT, 1996, 10 (14) :1773-1782
[10]   PREVENTION OF APOPTOSIS BY A BACULOVIRUS GENE DURING INFECTION OF INSECT CELLS [J].
CLEM, RJ ;
FECHHEIMER, M ;
MILLER, LK .
SCIENCE, 1991, 254 (5036) :1388-1390