Hippo signaling instructs ectopic but not normal organ growth

Science. 2022 Nov 18;378(6621):eabg3679. doi: 10.1126/science.abg3679. Epub 2022 Nov 18.

Abstract

The Hippo signaling pathway is widely considered a master regulator of organ growth because of the prominent overgrowth phenotypes caused by experimental manipulation of its activity. Contrary to this model, we show here that removing Hippo transcriptional output did not impair the ability of the mouse liver and Drosophila eyes to grow to their normal size. Moreover, the transcriptional activity of the Hippo pathway effectors Yap/Taz/Yki did not correlate with cell proliferation, and hyperactivation of these effectors induced gene expression programs that did not recapitulate normal development. Concordantly, a functional screen in Drosophila identified several Hippo pathway target genes that were required for ectopic overgrowth but not normal growth. Thus, Hippo signaling does not instruct normal growth, and the Hippo-induced overgrowth phenotypes are caused by the activation of abnormal genetic programs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster* / embryology
  • Drosophila melanogaster* / genetics
  • Eye* / embryology
  • Gene Expression Regulation, Developmental*
  • Hippo Signaling Pathway* / genetics
  • Liver* / embryology
  • Mice
  • Organ Size
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Trans-Activators / genetics
  • Transcription, Genetic*
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins* / metabolism
  • YAP-Signaling Proteins* / metabolism

Substances

  • Drosophila Proteins
  • Protein Serine-Threonine Kinases
  • Trans-Activators
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • YAP-Signaling Proteins