title: Ccdc80-l1 Is involved in axon pathfinding of zebrafish motoneurons.
abstract: Axon pathfinding is a subfield of neural development by which neurons send out axons to reach the correct targets. In particular, motoneurons extend their axons toward skeletal muscles, leading to spontaneous motor activity. In this study, we identified the zebrafish Ccdc80 and Ccdc80-like1 (Ccdc80-l1) proteins in silico on the basis of their high aminoacidic sequence identity with the human CCDC80 (Coiled-Coil Domain Containing 80). We focused on ccdc80-l1 gene that is expressed in nervous and non-nervous tissues, in particular in territories correlated with axonal migration, such as adaxial cells and muscle pioneers. Loss of ccdc80-l1 in zebrafish embryos induced motility issues, although somitogenesis and myogenesis were not impaired. Our results strongly suggest that ccdc80-l1 is involved in axon guidance of primary and secondary motoneurons populations, but not in their proper formation. ccdc80-l1 has a differential role as regards the development of ventral and dorsal motoneurons, and this is consistent with the asymmetric distribution of the transcript. The axonal migration defects observed in ccdc80-l1 loss-of-function embryos are similar to the phenotype of several mutants with altered Hedgehog activity. Indeed, we reported that ccdc80-l1 expression is positively regulated by the Hedgehog pathway in adaxial cells and muscle pioneers. These findings strongly indicate ccdc80-l1 as a down-stream effector of the Hedgehog pathway.
authors.affiliation: Dipartimento di Biologia, Università degli Studi di Milano, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Brusegan
authors.forename: Anna
authors.initials: A
authors.lastname: Pistocchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Frassine
authors.forename: Isabella
authors.initials: I
authors.lastname: Della Noce
authors.forename: Filippo
authors.initials: F
authors.lastname: Schepis
authors.forename: Franco
authors.initials: F
authors.lastname: Cotelli
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation; D016678:Genome; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008954:Models, Biological; D009046:Motor Neurons / Q000502:physiology*; D024510:Muscle Development; D009132:Muscles / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D016415:Sequence Alignment; D019170:Somites / Q000502:physiology; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology; D014704:Veratrum Alkaloids / Q000494:pharmacology; D015027:Zebrafish
chemical_list: C492631:CCDC80 protein, human; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D014704:Veratrum Alkaloids; C000541:cyclopamine