Journal
DEVELOPMENTAL BIOLOGY
Volume 304, Issue 1, Pages 102-115Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2006.12.021
Keywords
Merlin; Expanded; Wingless; Hippo; apoptosis; tumor suppressor; cell cycle
Categories
Funding
- NCI NIH HHS [CA95281, P01 CA095281] Funding Source: Medline
- NIGMS NIH HHS [R01 GM055568, GM61672, GM55568, R01 GM061672] Funding Source: Medline
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Mutations that inactivate either merlin (mer) or expanded (ex) result in increased cell growth and proliferation in Drosophila. Both Mer and Ex are members of the Band 4.1 protein superfamily, and, based on analyses of mer ex double mutants, they are proposed to function together in at least a partially redundant manner upstream of the Hippo (Hpo) and Warts (Wts) proteins to regulate cell growth and division. By individually analyzing ex and mer mutant phenotypes, we have found important qualitative and quantitative differences in the ways Mer and Ex function to regulate cell proliferation and cell survival. Though both mer and ex restrict cell and tissue growth, ex clones exhibit delayed cell cycle exit in the developing eye, while mer clones do not. Conversely, loss of mer substantially compromises normal developmental apoptosis in the pupal retina, while loss of ex has only mild effects. Finally, ex has a role in regulating Wingless protein levels in the eye that is not obviously shared by either mer or hpo. Taken together, our data suggest that Mer and Ex differentially regulate multiple downstream pathways. (c) 2006 Elsevier Inc. All rights reserved.
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