The tumor suppressor gene fat modulates the EGFR-mediated proliferation control in the imaginal tissues of Drosophila melanogaster.
Molecules involved in cell adhesion can regulate both early signal transduction events, triggered by soluble factors, and downstream events involved in cell cycle progression. Correct integration of these signals allows appropriate cellular growth, differentiation and ultimately tissue morphogenesis, but incorrect interpretation contributes to pathologies such as tumor growth. The Fat cadherin is a tumor suppressor protein required in Drosophila for epithelial morphogenesis, proliferation control and epithelial planar polarization, and its loss results in a hyperplastic growth of imaginal tissues. While several molecular events have been characterized through which fat participates in the establishment of the epithelial planar polarity, little is known about mechanisms underlying fat-mediated control of cell proliferation. Here we provide evidence that fat specifically cooperates with the epidermal growth factor receptor (EGFR) pathway in controlling cell proliferation in developing imaginal epithelia. Hyperplastic larval and adult fat structures indeed undergo an amazing, synergistic enlargement following to EGFR oversignalling. We further show that such a strong functional interaction occurs downstream of MAPK activation through the transcriptional regulation of genes involved in the EGFR nuclear signalling. Considering that fat mutation shows di per se a hyperplastic phenotype, we suggest a model in which fat acts in parallel to EGFR pathway in transducing different cell communication signals; furthermore its function is requested downstream of MAPK for a correct rendering of the growth signals converging to the epidermal growth factor receptor.
Garoia
Flavio
F
Alma Mater Studiorum, Università di Bologna, CIRSA-GenMAP Lab, via S.Alberto 163, 48100 Ravenna, Italy. garoia@cib.unibo.it
Grifoni
Daniela
D
Trotta
Vincenzo
V
Guerra
Daniela
D
Pezzoli
Maria Cristina
MC
Cavicchi
Sandro
S
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003001:Cloning, Molecular; D018450:Disease Progression; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D008953:Models, Anatomic; D009154:Mutation; D010641:Phenotype; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic; D014921:Wings, Animal / Q000378:metabolism
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C472307:ft protein, Drosophila; D049452:Green Fluorescent Proteins; D066246:ErbB Receptors