Hippo signalling controls Dronc activity to regulate organ size in Drosophila.

Cell Death and Differentiation
S VergheseM Kango-Singh

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 contro...Continue Reading

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Citations

Mar 27, 2015·Wiley Interdisciplinary Reviews. Developmental Biology·Rewatee H Gokhale, Alexander W Shingleton
Dec 3, 2014·Developmental Biology·Hailey J KwonMadhuri Kango-Singh
Sep 30, 2020·Genesis : the Journal of Genetics and Development·Meghana TareAmit Singh
Feb 6, 2019·Scientific Reports·Orkhon TsogtbaatarKyung-Ok Cho
Mar 6, 2019·Nature Communications·Saoirse S McSharry, Greg J Beitel
Jun 25, 2019·Frontiers in Cell and Developmental Biology·Kirti SnigdhaMadhuri Kango-Singh
Jun 2, 2018·BioMed Research International·Derek Cui XuLuis Alberto Baena-Lopez
Oct 8, 2020·Genetics·Michael J TexadaKim Rewitz
Feb 10, 2021·G3 : Genes - Genomes - Genetics·Miles W DeAngelisRuth I Johnson
Oct 17, 2020·Neural Regeneration Research·Neha GogiaAmit Singh
May 7, 2021·Genetics·Michael J TexadaKim Rewitz
Jun 14, 2021·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Sicong ZhouJianhua Huang

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