title: JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling.
abstract: Components of the KDM7 family of histone demethylases are implicated in neuronal development and one member, PHF8, is often found to be mutated in cases of X-linked mental retardation. However, how PHF8 regulates neurodevelopmental processes and contributes to the disease is still largely unknown. Here, we show that the catalytic activity of a PHF8 homolog inCaenorhabditis elegans, JMJD-1.2, is required non-cell-autonomously for proper axon guidance. Loss of JMJD-1.2 dysregulates transcription of the Hedgehog-related geneswrt-8andgrl-16, the overexpression of which is sufficient to induce the axonal defects. Deficiency of eitherwrt-8orgrl-16, or reduced expression of homologs of genes promoting Hedgehog signaling, restores correct axon guidance injmjd-1.2mutants. Genetic and overexpression data indicate that Hedgehog-related genes act on axon guidance through actin remodelers. Thus, our study highlights a novel function ofjmjd-1.2in axon guidance that might be relevant for the onset of X-linked mental retardation and provides compelling evidence of a conserved function of the Hedgehog pathway inC. elegansaxon migration.
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200, Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, 2200, Copenhagen, Denmark.
authors.forename: Alba Redo
authors.initials: AR
authors.lastname: Riveiro
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200, Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, 2200, Copenhagen, Denmark.
authors.forename: Luca
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200, Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, 2200, Copenhagen, Denmark.
authors.forename: Emily
authors.initials: E
authors.lastname: Malmberg
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200, Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, 2200, Copenhagen, Denmark.
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Amendola
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, 70211, Kuopio, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Peltonen
authors.affiliation: Faculty of Health Sciences, University of Macau, 999078, Macau, China.
authors.forename: Garry
authors.initials: G
authors.lastname: Wong
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200, Copenhagen, Denmark lisa.salcini@bric.ku.dk.|Centre for Epigenetics, University of Copenhagen, 2200, Copenhagen, Denmark.
authors.forename: Anna Elisabetta
authors.identifier: 0000-0001-5828-2512
authors.initials: AE
authors.lastname: Salcini
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D000071437:Axon Guidance; D001369:Axons / Q000378:metabolism*; D064113:CRISPR-Cas Systems; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D056466:Histone Demethylases / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; D053823:Hedgehog Proteins; D056466:Histone Demethylases; C553255:JMJD-1.2 protein, C elegans; D056484:Jumonji Domain-Containing Histone Demethylases
keywords: Axon guidance; C. elegans; Epigenetics; Hedgehog signaling; Histone demethylase; Neuronal development