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Curr Biol. 2006 Nov 7;16(21):2101-10. Epub 2006 Oct 12.

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

Author information

1
Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.

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.

PMID:
17045801
DOI:
10.1016/j.cub.2006.09.045
[Indexed for MEDLINE]
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