title: Genetic dissection of photoreceptor subtype specification by the Drosophila melanogaster zinc finger proteins elbow and no ocelli.
abstract: The elbow/no ocelli (elb/noc) complex of Drosophila melanogaster encodes two paralogs of the evolutionarily conserved NET family of zinc finger proteins. These transcriptional repressors share a conserved domain structure, including a single atypical C2H2 zinc finger. In flies, Elb and Noc are important for the development of legs, eyes and tracheae. Vertebrate NET proteins play an important role in the developing nervous system, and mutations in the homolog ZNF703 human promote luminal breast cancer. However, their interaction with transcriptional regulators is incompletely understood. Here we show that loss of both Elb and Noc causes mis-specification of polarization-sensitive photoreceptors in the 'dorsal rim area' (DRA) of the fly retina. This phenotype is identical to the loss of the homeodomain transcription factor Homothorax (Hth)/dMeis. Development of DRA ommatidia and expression of Hth are induced by the Wingless/Wnt pathway. Our data suggest that Elb/Noc genetically interact with Hth, and we identify two conserved domains crucial for this function. Furthermore, we show that Elb/Noc specifically interact with the transcription factor Orthodenticle (Otd)/Otx, a crucial regulator of rhodopsin gene transcription. Interestingly, different Elb/Noc domains are required to antagonize Otd functions in transcriptional activation, versus transcriptional repression. We propose that similar interactions between vertebrate NET proteins and Meis and Otx factors might play a role in development and disease.
authors.affiliation: Center for Developmental Genetics, Department of Biology, New York University, New York, New York, United States of America; Department of Neurobiology, Stanford University, Stanford, California, United States of America.
authors.forename: Mathias F
authors.initials: MF
authors.lastname: Wernet
authors.affiliation: Center for Developmental Genetics, Department of Biology, New York University, New York, New York, United States of America.
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Meier
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Baumann-Klausener
authors.affiliation: Geneyouin Inc., Maple, Ontario, Canada.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Dorfman
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Weihe
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Labhart
authors.affiliation: Center for Developmental Genetics, Department of Biology, New York University, New York, New York, United States of America.
authors.forename: Claude
authors.initials: C
authors.lastname: Desplan
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000254:growth & development / Q000378:metabolism; D012243:Rhodopsin / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C465760:ElB protein, Drosophila; D018398:Homeodomain Proteins; C085456:Noc protein, Drosophila; D009687:Nuclear Proteins; D014157:Transcription Factors; C093053:oc protein, Drosophila; D012243:Rhodopsin