Maintenance of Cell Fate by the Polycomb Group Gene Sex Combs Extra Enables a Partial Epithelial Mesenchymal Transition in Drosophila
Grace Jefferies, Jason Somers, Isabelle Lohrey, Vishal Chaturvedi, Jacob Calabria, Owen J Marshall, Tony D Southall, Robert Saint, Michael J Murray
G3-GENES GENOMES GENETICS | GENETICS SOCIETY AMERICA | Published : 2020
Epigenetic silencing by Polycomb group (PcG) complexes can promote epithelial-mesenchymal transition (EMT) and stemness and is associated with malignancy of solid cancers. Here we report a role for Drosophila PcG repression in a partial EMT event that occurs during wing disc eversion, an early event during metamorphosis. In a screen for genes required for eversion we identified the PcG genes Sex combs extra (Sce) and Sex combs midleg ( Scm). Depletion of Sce or Scm resulted in internalized wings and thoracic clefts, and loss of Sce inhibited the EMT of the peripodial epithelium and basement membrane breakdown, ex vivo. Targeted DamID (TaDa) using Dam-Pol II showed that Sce knockdown caused ..View full abstract
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Awarded by National Health and Medical Research Council Project Grant
Awarded by Wellcome Trust Investigator grant
We are grateful to following people for fly stocks and reagents: L. S. Shashidhara for the Ubx-GAL4 stock, B. Gebelein for anti-abd-A, F. Maschat for anti-Fra, J. Muller for the Sce<SUP>KO</SUP> flies, M. Vidal for anti-Sce, F. J. Diaz-Benjumea for anti-Nubbin, M. D. Biggin for anti-Caudal, The Bloomington Drosophila Stock Centre, DGRC and the Vienna Drosophila Research Centre for fly stocks, the Developmental Studies Hybridoma Bank for antibodies. Next Generation sequencing performed by Stephen Wilcox at the Ian Potter Centre for Genomics within the Walter and Eliza Hall Institute for Medical Research, Victoria Australia, and the Australian Genome Research Facility, Victoria Australia. We are very grateful to A. Williams and Y. Melia for help with DamID and RNAi rescue cross experiments respectively, S. Wilcox for assistance with Genome Library preparation, The University of Melbourne Biological Optical Microscopy Platform, and the Monash University OzDros fly importation service. This work was supported by a National Breast Cancer Foundation Collaborative Breast Cancer Research Grant, a University of Melbourne MRGSS grant and a National Health and Medical Research Council Project Grant (GNT1107123) to M.J.M, a National Health and Medical Research Council Project Grant (APP1128784) to O.J.M. and a Wellcome Trust Investigator grant 104567/Z/14/Z to T.D.S.