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Article
Hippo Signalling Controls Dronc Activity to Regulate Organ Size in Drosophila
Cell Death and Differentiation
  • Shilpi Verghese, University of Dayton
  • Shimpi Bedi, University of Dayton
  • Madhuri Kango-Singh, University of Dayton
Document Type
Article
Publication Date
10-1-2012
Abstract

The Hippo pathway controls organ size by multiple mechanisms that ultimately regulate the transcriptional co-activator Yorkie (Yki). Downregulation of Hippo signalling leads to tissue overgrowths due to Yki-mediated activation of target genes, whereas overexpression of the pathway triggers apoptosis in developing tissues. However, the mechanism underlying cell death induced by Hippo (Hpo)-activation is not understood. We found that overexpression of Hpo leads to induction of Dronc (Drosophila Caspase-9 homologue) expression and downregulation of dronc can suppress/block Hpo-mediated apoptosis. Furthermore, upregulation of Dronc activity strongly suppressed the overgrowth caused by Yki overexpression thereby suggesting that Hippo signalling restricts Dronc activity. Hippo-mediated cell death requires the activity of the initiator caspase Dronc. Loss-of-function of dronc in genetic mosaics leads to cell survival and increased cell proliferation in imaginal discs. dronc is transcriptionally suppressed in Yki overexpressing cells or cells mutant for other Hippo pathway components like warts (wts). We propose that Dronc is a transcriptional target of the Hippo signalling pathway. The Hippo–Dronc connection has implications in control of overall organ size and other growth regulatory mechanisms like compensatory proliferation and cell competition.

Inclusive pages
1664–1676
ISBN/ISSN
1350-9047
Comments

Permission documentation on file.

Publisher
Nature Publishing Group
Peer Reviewed
Yes
Citation Information
Shilpi Verghese, Shimpi Bedi and Madhuri Kango-Singh. "Hippo Signalling Controls Dronc Activity to Regulate Organ Size in Drosophila" Cell Death and Differentiation Vol. 19 Iss. 10 (2012)
Available at: http://works.bepress.com/madhuri_kango-singh/33/