Copeland, Jeffrey M. and Bosdet, Ian and Freeman, J. Douglas and Guo, Ming and Gorski, Sharon M. and Hay, Bruce A. (2007) echinus, required for interommatidial cell sorting and cell death in the Drosophila pupal retina, encodes a protein with homology to ubiquitin-specific proteases. BMC Developmental Biology, 7 (82). ISSN 1471-213X http://resolver.caltech.edu/CaltechAUTHORS:COPbmcdb07p
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Background: Programmed cell death is used to remove excess cells between ommatidia in the Drosophila pupal retina. This death is required to establish the crystalline, hexagonal packing of ommatidia that characterizes the adult fly eye. In previously described echinus mutants, interommatidial cell sorting, which precedes cell death, occurred relatively normally. Interommatidial cell death was partially suppressed, resulting in adult eyes that contained excess pigment cells, and in which ommatidia were mildly disordered. These results have suggested that echinus functions in the pupal retina primarily to promote interommatidial cell death. Results: We generated a number of new echinus alleles, some of which are likely null mutants. Analysis of these alleles provides evidence that echinus has roles in cell sorting as well as cell death. echinus encodes a protein with homology to ubiquitin-specific proteases, which cleave ubiquitin-conjugated proteins at the ubiquitin C-terminus. The echinus locus encodes multiple splice forms, including two proteins that lack residues thought to be critical for deubiquitination activity. Surprisingly, ubiquitous expression in the eye of versions of Echinus that lack residues critical for ubiquitin specific protease activity, as well as a version predicted to be functional, rescue the echinus loss-of-function phenotype. Finally, genetic interactions were not detected between echinus loss and gain-of-function and a number of known apoptotic regulators. These include Notch, EGFR, the caspases Dronc, Drice, Dcp-1, Dream, the caspase activators, Rpr, Hid, and Grim, the caspase inhibitor DIAP1, and Lozenge or Klumpfuss. Conclusions: The echinus locus encodes multiple splice forms of a protein with homology to ubiquitin-specific proteases, but protease activity is unlikely to be required for echinus function, at least when echinus is overexpressed. Characterization of likely echinus null alleles and genetic interactions suggests that echinus acts at a novel point(s) to regulate interommatidial cell sorting and/or cell death in the fly eye.
|Additional Information:||© 2007 Copeland et al., licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Submission date 18 January 2007; Acceptance date 5 July 2007; Publication date 5 July 2007 Authors' contributions : JMC carried out most of the experiments in this study. IB and JDF isolated and sequenced echinus alleles, and carried out tissue-in-situ hybridization and RTPCR analysis of echinus expression. MG participated in data analysis, experimental design and writing of manuscript. SG and BAH were responsible for overall experiment design, analysis of data and, in conjunction with JMC, writing of the manuscript. All authors read and approved the final manuscript. Acknowledgements: We thank Burke Judd and Helmut Kramer for sharing unpublished information, Helmut Kramer and Ting Wu for echinus stocks, and Marco Marra for helpful discussions. SG is grateful to the BC Cancer Foundation and NSERC (Discovery Grant #250125 to M. Marra) for financial support. Financial support was provided by NIH grant GM057422 to B.A.H. and by NIH grants NS042580 and NS048396 to M.G.|
|Official Citation:||Jeffrey M Copeland, Ian Bosdet, J Douglas Freeman, Ming Guo, Sharon M Gorski, and Bruce A Hay (2007) Echinus, required for interommatidial cell sorting and cell death in the Drosophila pupal retina, encodes a protein with homology to ubiquitin-specific proteases. BMC Developmental Biology, 7 (82), 5 July 2007. doi:10.1186/1471-213X-7-82|
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|Deposited On:||25 Jul 2007|
|Last Modified:||26 Dec 2012 09:36|
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