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A pathway of signals regulating effector and initiator caspases in the developing Drosophila eye

Yu, Sun-Yun and Yoo, Soon Ji and Yang, Lihui and Zapata, Cynthia and Srinivasan, Anu and Hay, Bruce A. and Baker, Nicholas E. (2002) A pathway of signals regulating effector and initiator caspases in the developing Drosophila eye. Development, 129 (13). pp. 3269-3278. ISSN 0950-1991.

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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.

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Additional Information:© 2002 The Company of Biologists Limited. Accepted 22 April 2002. We thank R. Cagan, H. Steller, C. Wesley, K. White and the Bloomington Drosophila Stock Center for genetic strains, K. White for permission to cite unpublished results, and A. Koyama and B. Mollereau for comments on the manuscript. These experiments were initiated after suggestions from R. Kitsis. Supported by the NIH grants GM47892 to N.E.B. and GM57422 to B.A.H. Confocal facilities provided by AIF, AECOM.
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Subject Keywords:Drosophila eye, Caspase, Drice, Dronc, Notch, EGF receptor, Hid, IAP, Apoptosis
Issue or Number:13
Record Number:CaltechAUTHORS:YUSdev02
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12703
Deposited By: Archive Administrator
Deposited On:20 Dec 2008 08:58
Last Modified:21 Apr 2020 19:04

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