Abstract
Canalization, also known as developmental robustness, describes an organism's ability to produce the same phenotype despite genotypic variations and environmental influences1,2. In Drosophila, Hsp90, the trithorax-group proteins and transposon silencing have been previously implicated in canalization3,4. Despite this, the molecular mechanism underlying canalization remains elusive. Here using a Drosophila eye-outgrowth assay sensitized by the dominant Krirregular facets-1(KrIf-1) allele3, we show that the Piwi-interacting RNA (piRNA) pathway, but not the short interfering RNA or micro RNA pathway, is involved in canalization. Furthermore, we isolated a protein complex composed of Hsp90, Piwi and Hop, the Hsp70/Hsp90 organizing protein homolog, and we demonstrated the function of this complex in canalization. Our data indicate that Hsp90 and Hop regulate the piRNA pathway through Piwi to mediate canalization. Moreover, they point to epigenetic silencing of the expression of existing genetic variants and the suppression of transposon-induced new genetic variation as two major mechanisms underlying piRNA pathway-mediated canalization.
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Acknowledgements
We thank the Siomi Lab for Piwi, Aub, and Ago 3 antibodies; R. Carthew and Y. Sik-Lee for FRT-dcr-1/2 flies and M. Chinkers for the Hop antibody. We would also like to thank L. Liu and V. Shteyn for technical assistance; A. Szakmary for Piwi position effect variegation (PEV) assay (Supplementary Fig. 3b), the Lin lab members for their valuable comments and A. Horwich for stimulating discussion. This work is supported by the US National Institutes of Health Grant R01HD33760, the G. Harold and Leila Mathers Foundation and the Connecticut Stem Cell Research Fund (06SCD01, 06SCE01 and 08SCD-Yale-004) to H.L.
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V.K.G. and H.L. designed the project and wrote the paper. H.Y. made the initial observation that piwi mutations affect canalization. M.M.W. showed that Hop mutations enhance eye outgrowth phenotype. J.W. performed two-dimensional gel electrophoresis and X.A.H. assisted with column chromatography.
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Supplementary Figures 1–4 and Supplementary Table 1 (PDF 7205 kb)
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Gangaraju, V., Yin, H., Weiner, M. et al. Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation. Nat Genet 43, 153–158 (2011). https://doi.org/10.1038/ng.743
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DOI: https://doi.org/10.1038/ng.743
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