The retinal determination gene Dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex

Development
Catarina Brás-PereiraFlorence Janody

Abstract

The Drosophila transcriptional co-activator protein Yorkie and its vertebrate orthologs YAP and TAZ are potent oncogenes, whose activity is normally kept in check by the upstream Hippo kinase module. Upon its translocation into the nucleus, Yorkie forms complexes with several tissue-specific DNA-binding partners, which help to define the tissue-specific target genes of Yorkie. In the progenitor cells of the eye imaginal disc, the DNA-binding transcription factor Homothorax is required for Yorkie-promoted proliferation and survival through regulation of the bantam microRNA (miRNA). The transit from proliferating progenitors to cell cycle quiescent precursors is associated with the progressive loss of Homothorax and gain of Dachshund, a nuclear protein related to the Sno/Ski family of co-repressors. We have identified Dachshund as an inhibitor of Homothorax-Yorkie-mediated cell proliferation. Loss of dachshund induces Yorkie-dependent tissue overgrowth. Conversely, overexpressing dachshund inhibits tissue growth, prevents Yorkie or Homothorax-mediated cell proliferation of disc epithelia and restricts the transcriptional activity of the Yorkie-Homothorax complex on the bantam enhancer in Drosophila cells. In addition, Dachshund c...Continue Reading

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Citations

Jul 22, 2016·PLoS Genetics·Catarina Brás-PereiraFlorence Janody
Aug 11, 2018·Journal of Cellular Physiology·Jing-Yi ZhuJian Ye
Nov 6, 2018·Human Genetics·Pedro GasparAlistair P McGregor

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