The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling.
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.
Pellock
Brett J
BJ
Massachusetts General Hospital Cutaneous Biology Research Center, Charlestown, MA 02129, and University of California, Berkeley, Department of Molecular and Cell Biology 94720, USA.
Buff
Eugene
E
White
Kristin
K
Hariharan
Iswar K
IK
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000502:physiology*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D025581:Neurofibromin 2 / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D008565:Membrane Proteins; D025581:Neurofibromin 2; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C085090:ex protein, Drosophila; C099885:merlin, Drosophila; C074622:wg protein, Drosophila; D001973:Bromodeoxyuridine