title: The Drosophila ortholog of the Zc3h14 RNA binding protein acts within neurons to pattern axon projection in the developing brain.
abstract: The dNab2 polyadenosine RNA binding protein is the D. melanogaster ortholog of the vertebrate ZC3H14 protein, which is lost in a form of inherited intellectual disability (ID). Human ZC3H14 can rescue D. melanogaster dNab2 mutant phenotypes when expressed in all neurons of the developing nervous system, suggesting that dNab2/ZC3H14 performs well-conserved roles in neurons. However, the cellular and molecular requirements for dNab2/ZC3H14 in the developing nervous system have not been defined in any organism. Here we show that dNab2 is autonomously required within neurons to pattern axon projection from Kenyon neurons into the mushroom bodies, which are required for associative olfactory learning and memory in insects. Mushroom body axons lacking dNab2 project aberrantly across the brain midline and also show evidence of defective branching. Coupled with the prior finding that ZC3H14 is highly expressed in rodent hippocampal neurons, this requirement for dNab2 in mushroom body neurons suggests that dNab2/ZC3H14 has a conserved role in supporting axon projection and branching. Consistent with this idea, loss of dNab2 impairs short-term memory in a courtship conditioning assay. Taken together these results reveal a cell-autonomous requirement for the dNab2 RNA binding protein in mushroom body development and provide a window into potential neurodevelopmental functions of the human ZC3H14 protein.
authors.affiliation: Department of Biology, College of Wooster, Wooster, Ohio, 44691.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Kelly
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322.|Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, 30322.|Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, Georgia, 30322.
authors.forename: Rick
authors.initials: R
authors.lastname: Bienkowski
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Ayan
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19104.
authors.forename: David J
authors.initials: DJ
authors.lastname: Melicharek
authors.affiliation: Department of Biology, College of Wooster, Wooster, Ohio, 44691.
authors.forename: Zachariah A
authors.initials: ZA
authors.lastname: Brewer
authors.affiliation: Department of Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19104.|Departments of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19104.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Marenda
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Anita H
authors.initials: AH
authors.lastname: Corbett
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Moberg
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012313:RNA / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C578708:Nab2 protein, Drosophila; D016601:RNA-Binding Proteins; D012313:RNA
keywords: Drosophila; dNab2; mushroom body development; polyadenosine RNA binding protein