title: Insulin receptor-mediated signaling via phospholipase C-γ regulates growth and differentiation in Drosophila.
abstract: Coordination between growth and patterning/differentiation is critical if appropriate final organ structure and size is to be achieved. Understanding how these two processes are regulated is therefore a fundamental and as yet incompletely answered question. Here we show through genetic analysis that the phospholipase C-γ (PLC-γ) encoded by small wing (sl) acts as such a link between growth and patterning/differentiation by modulating some MAPK outputs once activated by the insulin pathway; particularly, sl promotes growth and suppresses ectopic differentiation in the developing eye and wing, allowing cells to attain a normal size and differentiate properly. sl mutants have previously been shown to have a combination of both growth and patterning/differentiation phenotypes: small wings, ectopic wing veins, and extra R7 photoreceptor cells. We show here that PLC-γ activated by the insulin pathway participates broadly and positively during cell growth modulating EGF pathway activity, whereas in cell differentiation PLC-γ activated by the insulin receptor negatively regulates the EGF pathway. These roles require different SH2 domains of PLC-γ, and act via classic PLC-γ signaling and EGF ligand processing. By means of PLC-γ, the insulin receptor therefore modulates differentiation as well as growth. Overall, our results provide evidence that PLC-γ acts during development at a time when growth ends and differentiation begins, and is important for proper coordination of these two processes.
authors: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México Campus Juriquilla, Querétaro, Querétaro, México.
authors: Juan M
authors: JM
authors: Murillo-Maldonado
authors: Fouad Bou
authors: FB
authors: Zeineddine
authors: Rachel
authors: R
authors: Stock
authors: Justin
authors: J
authors: Thackeray
authors: Juan R
authors: JR
authors: Riesgo-Escovar
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development* / Q000648:ultrastructure; D005123:Eye / Q000033:anatomy & histology / Q000166:cytology / Q000648:ultrastructure; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D017344:Genes, Insect / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009929:Organ Size; D010641:Phenotype; D051966:Phospholipase C gamma / Q000737:chemistry / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014921:Wings, Animal / Q000166:cytology / Q000201:enzymology / Q000254:growth & development
chemical_list: D029721:Drosophila Proteins; D011972:Receptor, Insulin; D051966:Phospholipase C gamma; C117088:SL protein, Drosophila