title: A Drosophila gain-of-function screen for candidate genes involved in steroid-dependent neuroendocrine cell remodeling.
abstract: The normal functioning of neuroendocrine systems requires that many neuropeptidergic cells change, to alter transmitter identity and concentration, electrical properties, and cellular morphology in response to hormonal cues. During insect metamorphosis, a pulse of circulating steroids, ecdysteroids, governs the dramatic remodeling of larval neurons to serve adult-specific functions. To identify molecular mechanisms underlying metamorphic remodeling, we conducted a neuropeptidergic cell-targeted, gain-of-function genetic screen. We screened 6097 lines. Each line permitted Gal4-regulated transcription of flanking genes. A total of 58 lines, representing 51 loci, showed defects in neuropeptide-mediated developmental transitions (ecdysis or wing expansion) when crossed to the panneuropeptidergic Gal4 driver, 386Y-Gal4. In a secondary screen, we found 29 loci that produced wing expansion defects when crossed to a crustacean cardioactive peptide (CCAP)/bursicon neuron-specific Gal4 driver. At least 14 loci disrupted the formation or maintenance of adult-specific CCAP/bursicon cell projections during metamorphosis. These include components of the insulin and epidermal growth factor signaling pathways, an ecdysteroid-response gene, cabut, and an ubiquitin-specific protease gene, fat facets, with known functions in neuronal development. Several additional genes, including three micro-RNA loci and two factors related to signaling by Myb-like proto-oncogenes, have not previously been implicated in steroid signaling or neuronal remodeling.
authors.affiliation: Department of Zoology, University of Oklahoma, Norman, Oklahoma 73019, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhao
authors.forename: Tingting
authors.initials: T
authors.lastname: Gu
authors.forename: Heather C
authors.initials: HC
authors.lastname: Rice
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: McAdams
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Roark
authors.forename: Kaylan
authors.initials: K
authors.lastname: Lawson
authors.forename: Sebastien A
authors.initials: SA
authors.lastname: Gauthier
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Reagan
authors.forename: Randall S
authors.initials: RS
authors.lastname: Hewes
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004251:DNA Transposable Elements; D004331:Drosophila melanogaster / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D017403:In Situ Hybridization; D009490:Neurosecretory Systems / Q000502:physiology*; D012313:RNA / Q000235:genetics; D013256:Steroids / Q000502:physiology*; D019076:Transgenes
chemical_list: D004251:DNA Transposable Elements; D013256:Steroids; D012313:RNA; D004247:DNA