Spontaneous motor-behavior abnormalities in two models of neurodevelopmental disorders
AuthorAndrew, David R
Moe, Mariah E
Tello, Judith A
Doser, Rachel L
Conner, William E
Ghuman, Jaswinder K
Restifo, Linda L
AffiliationUniv Arizona Hlth Sci, Dept Neurol
Univ Arizona, Ctr Insect Sci
Univ Arizona, Grad Interdisciplinary Program Neurosci
Univ Arizona Hlth Sci, Dept Psychiat
Univ Arizona, BIO5 Interdisciplinary Res Inst
MetadataShow full item record
PublisherTAYLOR & FRANCIS LTD
CitationDavid R. Andrew, Mariah E. Moe, Dailu Chen, Judith A. Tello, Rachel L. Doser, William E. Conner, Jaswinder K. Ghuman & Linda L. Restifo (2020): Spontaneous motor-behavior abnormalities in two Drosophila models of neurodevelopmental disorders, Journal of Neurogenetics, DOI: 10.1080/01677063.2020.1833005
JournalJournal of neurogenetics
Rights© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractMutations in hundreds of genes cause neurodevelopmental disorders with abnormal motor behavior alongside cognitive deficits. Boys with fragile X syndrome (FXS), a leading monogenic cause of intellectual disability, often display repetitive behaviors, a core feature of autism. By direct observation and manual analysis, we characterized spontaneous-motor-behavior phenotypes of Drosophila dfmr1 mutants, an established model for FXS. We recorded individual 1-day-old adult flies, with mature nervous systems and prior to the onset of aging, in small arenas. We scored behavior using open-source video-annotation software to generate continuous activity timelines, which were represented graphically and quantitatively. Young dfmr1 mutants spent excessive time grooming, with increased bout number and duration; both were rescued by transgenic wild-type dfmr1+ . By two grooming-pattern measures, dfmr1-mutant flies showed elevated repetitions consistent with perseveration, which is common in FXS. In addition, the mutant flies display a preference for grooming posterior body structures, and an increased rate of grooming transitions from one site to another. We raise the possibility that courtship and circadian rhythm defects, previously reported for dfmr1 mutants, are complicated by excessive grooming. We also observed significantly increased grooming in CASK mutants, despite their dramatically decreased walking phenotype. The mutant flies, a model for human CASK-related neurodevelopmental disorders, displayed consistently elevated grooming indices throughout the assay, but transient locomotory activation immediately after placement in the arena. Based on published data identifying FMRP-target transcripts and functional analyses of mutations causing human genetic neurodevelopmental disorders, we propose the following proteins as candidate mediators of excessive repetitive behaviors in FXS: CaMKIIα, NMDA receptor subunits 2A and 2B, NLGN3, and SHANK3. Together, these fly-mutant phenotypes and mechanistic insights provide starting points for drug discovery to identify compounds that reduce dysfunctional repetitive behaviors.
NoteOpen access article
VersionFinal published version
Except where otherwise noted, this item's license is described as © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
- Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase.
- Authors: Siller SS, Broadie K
- Issue date: 2011 Sep
- Wnd/DLK Is a Critical Target of FMRP Responsible for Neurodevelopmental and Behavior Defects in the Drosophila Model of Fragile X Syndrome.
- Authors: Russo A, DiAntonio A
- Issue date: 2019 Sep 3
- Elevated levels of the vesicular monoamine transporter and a novel repetitive behavior in the Drosophila model of fragile X syndrome.
- Authors: Tauber JM, Vanlandingham PA, Zhang B
- Issue date: 2011
- Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model.
- Authors: Monyak RE, Emerson D, Schoenfeld BP, Zheng X, Chambers DB, Rosenfelt C, Langer S, Hinchey P, Choi CH, McDonald TV, Bolduc FV, Sehgal A, McBride SMJ, Jongens TA
- Issue date: 2017 Aug
- Modeling Fragile X Syndrome in <i>Drosophila</i>.
- Authors: Drozd M, Bardoni B, Capovilla M
- Issue date: 2018