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Mutations in lozenge and D-Pax2 invoke ectopic patterned cell death in the developing Drosophila eye using distinct mechanisms

Development Genes and Evolution volume 213, pages 107–119 (2003)Cite this article

Abstract

Mutations in the lozenge gene of Drosophila melanogaster elicit a pleiotropic set of adult phenotypes, including severe compound eye perturbations resulting from the defective recruitment of photoreceptors R1/6 and R7, cone and pigment cells. In this study, we show that excessive patterned apoptosis is evident at the same developmental stage in these lozenge mutants. In lozenge null mutants, apoptosis occurs prior to lozenge-dependent cell fate specification. A second gene, D-Pax2, genetically interacts with lozenge. Interestingly, D-Pax2 mutants also exhibit increased cell death, but slightly later in development than that in lozenge mutants. Although expression of the caspase inhibitor p35 eliminates death in both lozenge and D-Pax2 mutants, the lozenge mutant eye phenotypes persist because other normal Lozenge functions are still lacking. D-Pax2 eye phenotypes, in contrast, are dramatically altered in a p35 background, because cells that normally differentiate as cone and primary pigment cells are subsequently transformed into secondary pigment cells. This study leads us to propose that Lozenge, aside from its known role in gene regulation of cell-specific transcription factors, is required to contribute to the repression of cell death mechanisms, creating a permissive environment for the survival of undifferentiated cells in early eye development. Lack of lozenge expression increases the likelihood that an undifferentiated cell will initiate its default death program and die prematurely. The ectopic cell death evident in D-Pax2 mutants appears to arise from the cell fate transformation of cone cells into secondary pigment cells, either autonomously or as a result of defective signalling.

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Acknowledgements

We appreciate the thoughtful comments provided by the anonymous referees. We also extend our gratitude to Dr. M. Green who generously provided insight and guidance. We thank the Drosophila Stock Center at the University of Indiana, Bloomington, the Mid-America Stock Center, Bowling Green, and Drs. R. Stocker and M. Green for many of the fly strains used in this study. Dr. H. Steller provided a rpr clone. Dr. Rubin provided strains expressing baculovirus p35. Elav antibody developed by G. Rubin was obtained from the Developmental Studies Hybridoma Bank maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA. Technical assistance was provided by J. Suhan for the thin tissue sectioning and aspects of electron microscopy. We are grateful to Dr. U. Banerjee for valuable discussion and for sharing fly strains and unpublished results. R. Selvaraju provided thoughtful commentary on the manuscript. This work was supported in part by Duquesne University of the Holy Ghost and the following grants: NIH Pre-doctoral fellowship 5T32GM08067–100031 to J.R.C.; to J.A.P SURG/HHMI Awards to undergraduate researchers at Carnegie Mellon University, NIH grant EY09093, NSF/STC grant BIR-8920118, March of Dimes Birth Defects Foundation FY93–1010; Carnegie Mellon University Faculty Development Awards; Samuel and Emma Winters Foundation; and international collaborative support from the NSF INT-9605205 and the University of Melbourne.

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Author notes

  1. Tara L. Cheung & John Archie Pollock

    Present address: Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282, USA

Affiliations

  1. Department of Genetics, University of Melbourne, Parkville, Victoria, Australia

    Nicole A. Siddall, Jason A. Fair & Philip Batterham

  2. University of West Florida, Pensacola, FL 32514, USA

    Kristina Jackson Behan

  3. Northwestern University Medical School, Chicago, IL 60611, USA

    Jennifer R. Crew

  4. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA

    Tara L. Cheung & John Archie Pollock

Authors
  1. Nicole A. Siddall
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  2. Kristina Jackson Behan
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  3. Jennifer R. Crew
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  4. Tara L. Cheung
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  5. Jason A. Fair
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  6. Philip Batterham
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  7. John Archie Pollock
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Correspondence to John Archie Pollock.

Additional information

K.J. Behan, J.R. Crew, and J.A. Pollock conducted aspects of this work in the Department of Biological Sciences, Carnegie Mellon University. Pittsburgh, PA

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Siddall, N.A., Behan, K.J., Crew, J.R. et al. Mutations in lozenge and D-Pax2 invoke ectopic patterned cell death in the developing Drosophila eye using distinct mechanisms. Dev Genes Evol 213, 107–119 (2003). https://doi.org/10.1007/s00427-003-0295-y

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  • DOI: https://doi.org/10.1007/s00427-003-0295-y

Keywords

  • Lozenge
  • D-Pax2
  • Atonal
  • Apoptosis
  • Caspase inhibitor p35