Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway

Curr Biol. 2006 Nov 7;16(21):2101-10. doi: 10.1016/j.cub.2006.09.045. Epub 2006 Oct 12.

Abstract

Background: The atypical Fat cadherin has long been known to control cell proliferation and organ size in Drosophila, but the mechanism by which Fat controls these processes has remained elusive. A newly emerging signaling pathway that controls organ size during development is the Salvador/Warts/Hippo pathway.

Results: Here we demonstrate that Fat limits organ size by modulating activity of the Salvador/Warts/Hippo pathway. ft interacts genetically with positive and negative regulators of this pathway, and tissue lacking fat closely phenocopies tissue deficient for genes that normally promote Salvador/Warts/Hippo pathway activity. Cells lacking fat grow and proliferate more quickly than their wild-type counterparts and exhibit delayed cell-cycle exit as a result of elevated expression of Cyclin E. fat mutant cells display partial insensitivity to normal developmental apoptosis cues and express increased levels of the anti-apoptotic DIAP1 protein. Collectively, these defects lead to increased organ size and organism lethality in fat mutant animals. Fat modulates Salvador/Warts/Hippo pathway activity by promoting abundance and localization of Expanded protein at the apical membrane of epithelial tissues.

Conclusions: Fat restricts organ size during Drosophila development via the Salvador/Warts/Hippo pathway. These studies aid our understanding of developmental organ size control and have implications for human hyperproliferative disorders, such as cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cadherins / genetics
  • Cadherins / physiology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology*
  • Cell Cycle
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation
  • Cyclin E
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Eye / anatomy & histology
  • Eye / embryology
  • Inhibitor of Apoptosis Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / metabolism
  • Organ Size
  • Phenotype
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Retina / cytology
  • Signal Transduction*
  • Wings, Animal / anatomy & histology

Substances

  • Cadherins
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Cyclin E
  • DIAP1 protein, Drosophila
  • Drosophila Proteins
  • Inhibitor of Apoptosis Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • ex protein, Drosophila
  • ft protein, Drosophila
  • sav protein, Drosophila
  • Protein Kinases
  • wts protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila