Distinct mechanisms of apoptosis-induced compensatory proliferation in proliferating and differentiating tissues in the Drosophila eye.
In multicellular organisms, apoptotic cells induce compensatory proliferation of neighboring cells to maintain tissue homeostasis. In the Drosophila wing imaginal disc, dying cells trigger compensatory proliferation through secretion of the mitogens Decapentaplegic (Dpp) and Wingless (Wg). This process is under control of the initiator caspase Dronc, but not effector caspases. Here we show that a second mechanism of apoptosis-induced compensatory proliferation exists. This mechanism is dependent on effector caspases which trigger the activation of Hedgehog (Hh) signaling for compensatory proliferation. Furthermore, whereas Dpp and Wg signaling is preferentially employed in apoptotic proliferating tissues, Hh signaling is activated in differentiating eye tissues. Interestingly, effector caspases in photoreceptor neurons stimulate Hh signaling which triggers cell-cycle reentry of cells that had previously exited the cell cycle. In summary, dependent on the developmental potential of the affected tissue, different caspases trigger distinct forms of compensatory proliferation in an apparent nonapoptotic function.
Fan
Yun
Y
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1000, Houston, TX 77030, USA.
Bergmann
Andreas
A
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005123:Eye / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C064196:dpp protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila; D020169:Caspases