title: Regulatory logic driving stable levels ofdefective proventriculusexpression during terminal photoreceptor specification in flies.
abstract: How differential levels of gene expression are controlled in post-mitotic neurons is poorly understood. In theDrosophilaretina, expression of the transcription factor Defective Proventriculus (Dve) at distinct cell type-specific levels is required for terminal differentiation of color- and motion-detecting photoreceptors. Here, we find that the activities of twocis-regulatory enhancers are coordinated to drivedveexpression in the fly eye. Three transcription factors act on these enhancers to determine cell-type specificity. Negative autoregulation by Dve maintains expression from each enhancer at distinct homeostatic levels. One enhancer acts as an inducible backup ('dark' shadow enhancer) that is normally repressed but becomes active in the absence of the other enhancer. Thus, two enhancers integrate combinatorial transcription factor input, feedback and redundancy to generate cell type-specific levels ofdveexpression and stable photoreceptor fate. This regulatory logic may represent a general paradigm for how precise levels of gene expression are established and maintained in post-mitotic neurons.
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Anderson
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Kayla
authors.initials: K
authors.lastname: Viets
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Sang
authors.initials: S
authors.lastname: Tran
authors.affiliation: Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Goldberg
authors.affiliation: Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Small
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2685, USA robertjohnston@jhu.edu.
authors.forename: Robert J
authors.identifier: 0000-0002-5775-6218
authors.initials: RJ
authors.lastname: Johnston
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006706:Homeostasis; D008938:Mitosis; D009474:Neurons / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D011531:Proventriculus / Q000196:embryology*; D012160:Retina / Q000196:embryology / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D012243:Rhodopsin
keywords: Dark shadow enhancer; Defective proventriculus; Drosophila retina; Orthodenticle; Photoreceptor; Rhodopsin; Shadow enhancer; Spalt; Spineless