title: SOCS36E specifically interferes with Sevenless signaling during Drosophila eye development.
abstract: During the development of multicellular organisms the fate of individual cells is specified with great precision and reproducibility. Although classical genetic approaches led to the identification of many of the signaling pathways contributing to cell fate specification, they have provided little insight into the mechanisms that ensure robustness and reproducibility. We have used the specification of the R7 photoreceptor cells controlled by the Sevenless receptor tyrosine kinase (Sev) pathway to screen for modulators of pathway activity and to uncover the mechanisms underlying the robustness of cell fate decisions. Here we provide genetic evidence that the Drosophila SOCS36E adaptor protein containing an SH2 domain and a SOCS box acts as an attenuator of Sev signaling. Overexpression of Socs36E strongly suppresses the specification of extra R7 photoreceptor cells in response to constitutive activation of Sev, and loss of Socs36E function suppresses the loss of R7 cells when Sev activity is impaired. In a wild-type background, however, loss and gain of Socs36E function exhibits little effect on R7 specification. We also show that SH2 domain of SOCS36E is essential for this function in inhibiting Sev action and that Socs36E expression is suppressed by high Sev pathway activity. In our model, only the cell able to activate high levels of receptor tyrosine kinase signaling will repress SOCS36E expression, reduce the negative effect on Sev signaling and allow this cell to differentiate into R7. In contrast, the remaining cells fail to receive high signaling, and thus maintain high levels of SOCS36E. This represses residual Sev activity and blocks R7 development. Therefore, Socs36E constitutes a novel partially redundant feedback mechanism that contributes to the robustness of R7 specification. The SOCS family of adaptor proteins may have evolved as modulators of specific signaling pathways that contribute to the robustness and precision of cell fate specification.
authors.affiliation: Departament de Genètica, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Almudi
authors.forename: Hugo
authors.initials: H
authors.lastname: Stocker
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
authors.forename: Montserrat
authors.initials: M
authors.lastname: Corominas
authors.forename: Florenci
authors.initials: F
authors.lastname: Serras
mesh_terms: D000818:Animals; D001483:Base Sequence; D002450:Cell Communication / Q000502:physiology; D054910:Compound Eye, Arthropod / Q000166:cytology / Q000254:growth & development*; D004330:Drosophila / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D009154:Mutation; D010786:Photoreceptor Cells / Q000502:physiology; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; C460659:Socs36E protein, Drosophila; D050826:Suppressor of Cytokine Signaling Proteins; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila