Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways.
In many metazoans, damaged and potentially dangerous cells are rapidly eliminated by apoptosis. In Drosophila, this is often compensated for by extraproliferation of neighboring cells, which allows the organism to tolerate considerable cell death without compromising development and body size. Despite its importance, the mechanistic basis of such compensatory proliferation remains poorly understood. Here, we show that apoptotic cells express the secretory factors wingless (wg) and decapentaplegic (dpp). When cells undergoing apoptosis were kept alive with the caspase inhibitor p35, excessive nonautonomous cell proliferation was observed. Significantly, wg signaling is necessary and, at least in some cells, also sufficient for mitogenesis under these conditions. Finally, we provide evidence that the DIAP1 antagonists reaper and hid can activate the JNK pathway and that this pathway is required for inducing wg and cell proliferation. These findings support a model where apoptotic cells activate signaling cascades for compensatory proliferation.
Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, Box 252, New York, NY 10021, USA.
Hyung Don
HD
Ryoo
Travis
T
Gorenc
Hermann
H
Steller
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D004330:Drosophila / Q000196:embryology / Q000254:growth & development; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000378:metabolism / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014921:Wings, Animal / Q000196:embryology / Q000254:growth & development; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D019476:Insect Proteins; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases