oxalylglycine and Eye-Abnormalities

RUGOSE (RG): encodes an A kinase anchor protein and was isolated as a genetic interactor of the Notch and epidermal growth factor receptor (EGFR) pathways during eye development in Drosophila. rg mutants display a small, rough eye phenotype primarily caused by the loss of cone cells. Here we show that the basis of this phenotype is cell type-specific apoptosis rather than transformation and hence can be rescued by reduction of proapoptotic signals. Moreover, a nearly complete rescue is observed by an increased Notch signal suggesting an antiapoptotic function of Notch in this developmental context. Cone cell loss in rg mutants is accompanied by enhanced Jun N-terminal kinase activity and, concomitantly, by a reduction of EGFR signalling activity. Together, these findings support the idea that rg plays an important role in the integration of different signals required for the exact regulation of cone cell development and survival.

Topics: A Kinase Anchor Proteins; Adaptor Proteins, Signal Transducing; Animals; Apoptosis; Cell Differentiation; Drosophila; Drosophila Proteins; ErbB Receptors; Eye; Eye Abnormalities; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Membrane Proteins; Mutation; Pupa; Receptors, Notch; Retina; Signal Transduction; Transcription Factors

Overexpression of Hairless (H) causes a remarkable degree of tissue loss and apoptosis during imaginal development. H functions as antagonist in the Notch-signaling pathway in Drosophila, and the link to growth and apoptosis is poorly understood. To further our insight into H-mediated apoptosis, we performed two large-scale screens for modifiers of a small rough eye phenotype caused by H overexpression. Both loss- and gain-of-function screens revealed known and new genetic interactors representing diverse cellular functions. Many of them did not cause eye phenotypes on their own, emphasizing a specific genetic interaction with H. As expected, we also identified components of different signaling pathways supposed to be involved in the regulation of cell growth and cell death. Accordingly, some of them also acted as modifiers of proapoptotic genes, suggesting a more general involvement in the regulation of apoptosis. Overall, these screens highlight the importance of H and the Notch pathway in mediating cell death in response to developmental and environmental cues and emphasize their role in maintaining developmental cellular homeostasis.

Topics: Animals; Apoptosis; Cell Differentiation; Cell Enlargement; Drosophila melanogaster; Drosophila Proteins; ErbB Receptors; Eye Abnormalities; Female; Inhibitor of Apoptosis Proteins; JNK Mitogen-Activated Protein Kinases; Male; Protein Kinases; Receptors, Invertebrate Peptide; Signal Transduction; Transcription Factors