Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations in Drosophila.
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.
Pérez-Garijo
Ainhoa
A
Centro de Biología Molecular CSIC-UAM, Universidad Autónoma de Madrid, Madrid 28049, Spain.
Martín
Francisco A
FA
Morata
Ginés
G
D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D019070:Cell Lineage; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D006358:Hot Temperature; D051034:Inhibitor of Apoptosis Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000002:abnormalities / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D051155:Wnt1 Protein
D061945:Caspase Inhibitors; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D011518:Proto-Oncogene Proteins; D014764:Viral Proteins; D051155:Wnt1 Protein; C064196:dpp protein, Drosophila; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; C074622:wg protein, Drosophila; D020169:Caspases