title: slc7a6os gene plays a critical role in defined areas of the developing CNS in zebrafish.
abstract: The aim of this study is to shed light on the functional role of slc7a6os, a gene highly conserved in vertebrates. The Danio rerio slc7a6os gene encodes a protein of 326 amino acids with 46% identity to human SLC7A6OS and 14% to Saccharomyces cerevisiae polypeptide Iwr1. Yeast Iwr1 specifically binds RNA pol II, interacts with the basal transcription machinery and regulates the transcription of specific genes. In this study we investigated for the first time the biological role of SLC7A6OS in vertebrates. Zebrafish slc7a6os is a maternal gene that is expressed throughout development, with a prevalent localization in the developing central nervous system (CNS). The gene is also expressed, although at different levels, in various tissues of the adult fish. To determine the functional role of slc7a6os during zebrafish development, we knocked-down the gene by injecting a splice-blocking morpholino. At 24 hpf morphants show morphological defects in the CNS, particularly the interface between hindbrain and midbrain is not well-defined. At 28 hpf the morpholino injected embryos present an altered somite morphology and appear partially or completely immotile. At this stage the midbrain, hindbrain and cerebellum are compromised and not well defined compared with control embryos. The observed alterations persist at later developmental stages. Consistently, the expression pattern of two markers specifically expressed in the developing CNS, pax2a and neurod, is significantly altered in morphants. The co-injection of embryos with synthetic slc7a6os mRNA, rescues the morphant phenotype and restores the wild type expression pattern of pax2a and neurod. Our data suggest that slc7a6os might play a critical role in defined areas of the developing CNS in vertebrates, probably by regulating the expression of key genes.
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Anna
authors: A
authors: Benini
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Francesca
authors: F
authors: Cignarella
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Laura
authors: L
authors: Calvarini
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Silvia
authors: S
authors: Mantovanelli
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Edoardo
authors: E
authors: Giacopuzzi
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Daniela
authors: D
authors: Zizioli
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Giuseppe
authors: G
authors: Borsani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D002490:Central Nervous System / Q000196:embryology* / Q000201:enzymology*; D019295:Computational Biology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C544940:IWR1 protein, S cerevisiae; D009419:Nerve Tissue Proteins; C551898:SLC7A6OS protein, human; C000605112:Slc7a6os protein, zebrafish; D029961:Zebrafish Proteins; D010447:Peptide Hydrolases