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.

FLAVIO GAROIA, DANIELA GRIFONI, VINCENZO TROTTA, DANIELA GUERRA, MARIA CRISTINA PEZZOLI, CAVICCHI S. (2005). The tumor suppressor gene fat modulates the EGFr-mediated proliferation control in the imaginal tissues of Drosophila melanogaster. MECHANISMS OF DEVELOPMENT, 122, 175-187 [10.1016/j.mod.2004.10.007].

The tumor suppressor gene fat modulates the EGFr-mediated proliferation control in the imaginal tissues of Drosophila melanogaster.

GAROIA, FLAVIO;GRIFONI, DANIELA;TROTTA, VINCENZO;GUERRA, DANIELA;PEZZOLI, MARIA CRISTINA;CAVICCHI, SANDRO
2005

Abstract

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.
2005
FLAVIO GAROIA, DANIELA GRIFONI, VINCENZO TROTTA, DANIELA GUERRA, MARIA CRISTINA PEZZOLI, CAVICCHI S. (2005). The tumor suppressor gene fat modulates the EGFr-mediated proliferation control in the imaginal tissues of Drosophila melanogaster. MECHANISMS OF DEVELOPMENT, 122, 175-187 [10.1016/j.mod.2004.10.007].
FLAVIO GAROIA; DANIELA GRIFONI; VINCENZO TROTTA; DANIELA GUERRA; MARIA CRISTINA PEZZOLI; CAVICCHI S.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/1222
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