title: The zebrafish orthologue of the dyslexia candidate gene DYX1C1 is essential for cilia growth and function.
abstract: DYX1C1, a susceptibility gene for dyslexia, encodes a tetratricopeptide repeat domain containing protein that has been implicated in neuronal migration in rodent models. The developmental role of this gene remains unexplored. To understand the biological function(s) of zebrafish dyx1c1 during embryonic development, we cloned the zebrafish dyx1c1 and used morpholino-based knockdown strategy. Quantitative real-time PCR analysis revealed the presence of dyx1c1 transcripts in embryos, early larval stages and in a wide range of adult tissues. Using mRNA in situ hybridization, we show here that dyx1c1 is expressed in many ciliated tissues in zebrafish. Inhibition of dyx1c1 produced pleiotropic phenotypes characteristically associated with cilia defects such as body curvature, hydrocephalus, situs inversus and kidney cysts. We also demonstrate that in dyx1c1 morphants, cilia length is reduced in several organs including Kupffer's vesicle, pronephros, spinal canal and olfactory placode. Furthermore, electron microscopic analysis of cilia in dyx1c1 morphants revealed loss of both outer (ODA) and inner dynein arms (IDA) that have been shown to be required for cilia motility. Considering all these results, we propose an essential role for dyx1c1 in cilia growth and function.
authors: Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors: Gayathri
authors: G
authors: Chandrasekar
authors: Liselotte
authors: L
authors: Vesterlund
authors: Kjell
authors: K
authors: Hultenby
authors: Isabel
authors: I
authors: Tapia-Páez
authors: Juha
authors: J
authors: Kere
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002923:Cilia / Q000378:metabolism* / Q000473:pathology; D003001:Cloning, Molecular; D004398:Dyneins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000473:pathology; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D007728:Kupffer Cells / Q000473:pathology; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics; D009928:Organ Specificity; D060910:Pronephros / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013115:Spinal Canal / Q000473:pathology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones; D060172:Morpholinos; D029961:Zebrafish Proteins; C584452:dnaaf4 protein, zebrafish; D004398:Dyneins
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