title: RBF and Rno promote photoreceptor differentiation onset through modulating EGFR signaling in the Drosophila developing eye.
abstract: The retinoblastoma gene Rb is the prototype tumor suppressor and is conserved in Drosophila. We use the developing fly retina as a model system to investigate the role of Drosophila Rb (rbf) during differentiation. This report shows that mutation of rbf and rhinoceros (rno), which encodes a PHD domain protein, leads to a synergistic delay in photoreceptor cell differentiation in the developing eye disc. We show that this differentiation delay phenotype is caused by decreased levels of different components of the Epidermal Growth Factor Receptor (EGFR) signaling pathway in the absence of rbf and rno. We show that rbf is required for normal expression of Rhomboid proteins and activation of MAP kinase in the morphogenetic furrow (MF), while rno is required for the expression of Pointed (Pnt) and Ebi proteins, which are key factors that mediate EGFR signaling output in the nucleus. Interestingly, while removing the transcription activation function of dE2F1 is sufficient to suppress the synergistic differentiation delay, a mutant form of de2f1 that disrupts the binding with RBF but retains the transcription activation function does not mimic the effect of rbf loss. These observations suggest that RBF has additional functions besides dE2F1 binding that regulates EGFR signaling and photoreceptor differentiation.
authors.affiliation: Ben May Institute for Cancer Research, Chicago, IL 60637, USA.
authors.forename: Madina J
authors.initials: MJ
authors.lastname: Sukhanova
authors.forename: Latishya J
authors.initials: LJ
authors.lastname: Steele
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhang
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Gordon
authors.forename: Wei
authors.initials: W
authors.lastname: Du
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000254:growth & development / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C496298:E2f1 protein, Drosophila; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C119014:ebi protein, Drosophila; C569495:rno protein, Drosophila; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins