title: The zinc finger RNA binding protein, ZFR, contributes to axon guidance in Caenorhabditis elegans.
abstract: ZFR is an ancient and highly conserved chromosome-associated protein from nematodes to mammals, embryologically expressed in most species, with the exception of the nematode Caenorhabditis elegans. The ZFR encodes zinc and RNA binding protein, and in rat, the nuclear-cytoplasmic shuttling ZFR has been found with transport and translation-associated RNA granule-like structures in the somatodendritic compartments of hippocampal neurons. The majority of axons cross the midline before projecting to their contralateral synaptic target and this crossing decision is under tight control. Molecular factors contributing to these processes have been identified, although the mechanisms are not fully understood. In this study, we tested the role of ceZFR in axon guidance using ceZfr RNAi-treated animals to analyse axon midline crossing, axon fasciculation and cord commissures. In adult stages, RNAi-induced depletion of the ceZfr transcript leads to several phenotypes related to axon guidance. A midline crossing defect was observed in the ventral nerve cord (VNC) in axon type D, DD/VD motoneuron axons and axon type 1, interneuron axons. We further detected a dorsal nerve cord (DNC) axon fasciculation. Some ceZfr RNAi-treated animals revealed that cord commissures fail to reach their synaptic target. We provide evidence that ceZFR has a role in axon guidance. When Zfr was depleted by RNAi, the phenotypes are characterized by defects in axon midline crossing, axon defasciculation and cord commissures. Our results thus support the hypothesis that ZFR has essential roles during neurogenesis, and could support early steps of RNA transport and localization through RNA granule formation in the nucleus and/or to their nucleo-cytoplasmic shuttling.
authors.affiliation: Aarhus University, Department of Biomedicine, Wilhelm Meyers Allé 4, DK-8000 Aarhus, Denmark.
authors.forename: Tine
authors.initials: T
authors.lastname: Kjærgaard
authors.affiliation: Aarhus University, Department of Molecular Biology and Genetics, Gustav Wieds Vej 10C, DK-8000 Aarhus, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Desdorf
authors.affiliation: Aarhus University, Department of Biomedicine, Wilhelm Meyers Allé 4, DK-8000 Aarhus, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Heuck
authors.affiliation: Aarhus University, Department of Molecular Biology and Genetics, Gustav Wieds Vej 10C, DK-8000 Aarhus, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Olsen
authors.affiliation: Aarhus University, Department of Biomedicine, Wilhelm Meyers Allé 4, DK-8000 Aarhus, Denmark. Electronic address: kly@biomed.au.dk.
authors.forename: Karin
authors.initials: K
authors.lastname: Lykke-Hartmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007395:Interneurons / Q000473:pathology; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics*; D034622:RNA Interference; D034443:RNA Transport / Q000502:physiology; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: D029742:Caenorhabditis elegans Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C554867:Y95B8A.8 protein, C elegans
keywords: Axon defasciculation and cord commissures; Axon guidance; C. elegans; ceZFR; ceZfr RNAi-induced axon midline crossing