title: ADrosophilamodel of Fragile X syndrome exhibits defects in phagocytosis by innate immune cells.
abstract: Fragile X syndrome, the most common known monogenic cause of autism, results from the loss of FMR1, a conserved, ubiquitously expressed RNA-binding protein. Recent evidence suggests that Fragile X syndrome and other types of autism are associated with immune system defects. We found thatDrosophila melanogaster Fmr1mutants exhibit increased sensitivity to bacterial infection and decreased phagocytosis of bacteria by systemic immune cells. Using tissue-specific RNAi-mediated knockdown, we showed that Fmr1 plays a cell-autonomous role in the phagocytosis of bacteria.Fmr1mutants also exhibit delays in two processes that require phagocytosis by glial cells, the immune cells in the brain: neuronal clearance after injury in adults and the development of the mushroom body, a brain structure required for learning and memory. Delayed neuronal clearance is associated with reduced recruitment of activated glia to the site of injury. These results suggest a previously unrecognized role for Fmr1 in regulating the activation of phagocytic immune cells both in the body and the brain.
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
authors.forename: Reed M
authors.initials: RM
authors.lastname: O'Connor
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
authors.forename: Elizabeth F
authors.identifier: 0000-0002-4148-7957
authors.initials: EF
authors.lastname: Stone
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
authors.forename: Charlotte R
authors.identifier: 0000-0003-4622-4627
authors.initials: CR
authors.lastname: Wayne
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
authors.forename: Emily V
authors.initials: EV
authors.lastname: Marcinkevicius
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
authors.forename: Matt
authors.initials: M
authors.lastname: Ulgherait
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
authors.forename: Rebecca
authors.identifier: 0000-0002-0920-0004
authors.initials: R
authors.lastname: Delventhal
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Pantalia
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
authors.forename: Vanessa M
authors.identifier: 0000-0002-8852-3708
authors.initials: VM
authors.lastname: Hill
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10025.
authors.forename: Clarice G
authors.identifier: 0000-0001-7390-1692
authors.initials: CG
authors.lastname: Zhou
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10025.
authors.forename: Sophie
authors.initials: S
authors.lastname: McAllister
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10025.
authors.forename: Anna
authors.identifier: 0000-0002-5946-6572
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Ziegenfuss
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032.
authors.forename: Wesley B
authors.initials: WB
authors.lastname: Grueber
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032.
authors.forename: Julie C
authors.identifier: 0000-0001-8135-2072
authors.initials: JC
authors.lastname: Canman
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032 ms4095@cumc.columbia.edu.
authors.forename: Mimi M
authors.identifier: 0000-0002-2730-1765
authors.initials: MM
authors.lastname: Shirasu-Hiza
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000276:immunology / Q000378:metabolism; D004331:Drosophila melanogaster / Q000276:immunology* / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D005600:Fragile X Syndrome / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D024521:Mushroom Bodies / Q000276:immunology / Q000378:metabolism; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D034622:RNA Interference / Q000276:immunology; D016601:RNA-Binding Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D016601:RNA-Binding Proteins