title: IMP2 axonal localization, RNA interactome, and function in the development of axon trajectories.
abstract: RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurological disease. Developing axons provide a model well suited to the study of RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles in axon pathfinding. However, the RNA-binding proteins involved in axon pathfinding, and their corresponding mRNA targets, are still largely unknown. Here we find that the RNA-binding protein IMP2 (Igf2bp2) is strikingly enriched in developing axon tracts, including in spinal commissural axons. We used the HITS-CLIP approach to perform a genome-wide identification of RNAs that interact directly with IMP2 in the native context of developing mouse brain. This IMP2 interactome was highly enriched for mRNA targets related to axon guidance. Accordingly, IMP2 knockdown in the developing spinal cord led to strong defects in commissural axon trajectories at the midline intermediate target. These results reveal a highly distinctive axonal enrichment of IMP2, show that it interacts with a network of axon guidance-related mRNAs, and reveal that it is required for normal axon pathfinding during vertebrate development.
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Preitner
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Quan
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen Ø DK-2100, Denmark.
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA flanagan@hms.harvard.edu.
authors.forename: John G
authors.identifier: 0000-0003-1341-1848
authors.initials: JG
authors.lastname: Flanagan
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000235:genetics / Q000502:physiology; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D002642:Chick Embryo; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology*
chemical_list: C559768:IGF2BP2 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
keywords: Axon guidance; IMP2; Igf2bp2; RNA interactome; RNA-binding protein