title: Combinatorial signaling by the Frizzled/PCP and Egfr pathways during planar cell polarity establishment in the Drosophila eye.
abstract: Frizzled (Fz)/PCP signaling regulates planar, vectorial orientation of cells or groups of cells within whole tissues. Although Fz/PCP signaling has been analyzed in several contexts, little is known about nuclear events acting downstream of Fz/PCP signaling in the R3/R4 cell fate decision in the Drosophila eye or in other contexts. Here we demonstrate a specific requirement for Egfr-signaling and the transcription factors Fos (AP-1), Yan and Pnt in PCP dependent R3/R4 specification. Loss and gain-of-function assays suggest that the transcription factors integrate input from Fz/PCP and Egfr-signaling and that the ETS factors Pnt and Yan cooperate with Fos (and Jun) in the PCP-specific R3/R4 determination. Our data indicate that Fos (either downstream of Fz/PCP signaling or parallel to it) and Yan are required in R3 to specify its fate (Fos) or inhibit R4 fate (Yan) and that Egfr-signaling is required in R4 via Pnt for its fate specification. Taken together with previous work establishing a Notch-dependent Su(H) function in R4, we conclude that Fos, Yan, Pnt, and Su(H) integrate Egfr, Fz, and Notch signaling input in R3 or R4 to establish cell fate and ommatidial polarity.
authors.affiliation: Department of Developmental and Regenerative Biology, Mt. Sinai School of Medicine, Annenberg Bldg. 18-92, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Weber
authors.forename: Csilla
authors.initials: C
authors.lastname: Pataki
authors.forename: Jozsef
authors.initials: J
authors.lastname: Mihaly
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C076188:AOP protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D051157:Frizzled Receptors; C497759:N protein, Drosophila; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D018010:Receptors, Invertebrate Peptide; D051880:Receptors, Notch; D012097:Repressor Proteins; C088731:Su(H) protein, Drosophila; D014157:Transcription Factors; C058784:fz protein, Drosophila; C435749:kay protein, Drosophila; C083884:pnt protein, Drosophila; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors