The zebrafish orthologue of the dyslexia candidate gene DYX1C1 is essential for cilia growth and function

Gayathri Chandrasekar; Liselotte Vesterlund; Kjell Hultenby; Isabel Tapia-Páez; Juha Kere

doi:10.1371/journal.pone.0063123

The zebrafish orthologue of the dyslexia candidate gene DYX1C1 is essential for cilia growth and function

PLoS One. 2013 May 1;8(5):e63123. doi: 10.1371/journal.pone.0063123. Print 2013.

Authors

Gayathri Chandrasekar¹, Liselotte Vesterlund, Kjell Hultenby, Isabel Tapia-Páez, Juha Kere

Affiliation

¹ Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Base Sequence
Cilia / metabolism*
Cilia / pathology
Cloning, Molecular
Dyneins / metabolism
Embryo, Nonmammalian / abnormalities
Embryo, Nonmammalian / pathology
Gene Expression
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Kupffer Cells / pathology
Molecular Chaperones / genetics
Molecular Chaperones / metabolism*
Molecular Sequence Data
Morpholinos / genetics
Organ Specificity
Pronephros / metabolism
Pronephros / pathology
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Spinal Canal / pathology
Zebrafish / embryology
Zebrafish / genetics*
Zebrafish / metabolism
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism*

Substances

Molecular Chaperones
Morpholinos
Zebrafish Proteins
dnaaf4 protein, zebrafish
Dyneins

Grants and funding

This work was supported by Swedish Research Council (www.vr.se); Swedish Royal Bank Tercentennial Foundation, Swedish Brain Foundation (Hjärnfonden)(www.hjarnfonden.se); Knut and Alice Wallenberg Foundation (www.wallenberg.com); Center for Biosciences and Sigrid Jusélius Foundation(www.sigridjuselius.fi). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.