title: A pathway of signals regulating effector and initiator caspases in the developing Drosophila eye.
abstract: Regulated cell death and survival play important roles in neural development. Extracellular signals are presumed to regulate seven apparent caspases to determine the final structure of the nervous system. In the eye, the EGF receptor, Notch, and intact primary pigment and cone cells have been implicated in survival or death signals. An antibody raised against a peptide from human caspase 3 was used to investigate how extracellular signals controlled spatial patterning of cell death. The antibody crossreacted specifically with dying Drosophila cells and labelled the activated effector caspase Drice. It was found that the initiator caspase Dronc and the proapoptotic gene head involution defective were important for activation in vivo. Dronc may play roles in dying cells in addition to activating downstream effector caspases. Epistasis experiments ordered EGF receptor, Notch, and primary pigment and cone cells into a single pathway that affected caspase activity in pupal retina through hid and Inhibitor of Apoptosis Proteins. None of these extracellular signals appeared to act by initiating caspase activation independently of hid. Taken together, these findings indicate that in eye development spatial regulation of cell death and survival is integrated through a single intracellular pathway.
authors.affiliation: Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Sun-Yun
authors.initials: SY
authors.lastname: Yu
authors.forename: Soon Ji
authors.initials: SJ
authors.lastname: Yoo
authors.forename: Lihui
authors.initials: L
authors.lastname: Yang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Zapata
authors.forename: Anu
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hay
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Baker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D005123:Eye / Q000196:embryology* / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch; D012160:Retina / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D009479:Neuropeptides; D051880:Receptors, Notch; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C118731:dronc protein, Drosophila