title: Increased expression of the dyslexia candidate gene DCDC2 affects length and signaling of primary cilia in neurons.
abstract: DCDC2 is one of the candidate susceptibility genes for dyslexia. It belongs to the superfamily of doublecortin domain containing proteins that bind to microtubules, and it has been shown to be involved in neuronal migration. We show that the Dcdc2 protein localizes to the primary cilium in primary rat hippocampal neurons and that it can be found within close proximity to the ciliary kinesin-2 subunit Kif3a. Overexpression of DCDC2 increases ciliary length and activates Shh signaling, whereas downregulation of Dcdc2 expression enhances Wnt signaling, consistent with a functional role in ciliary signaling. Moreover, DCDC2 overexpression in C. elegans causes an abnormal neuronal phenotype that can only be seen in ciliated neurons. Together our results suggest a potential role for DCDC2 in the structure and function of primary cilia.
authors.affiliation: Research Program's Unit, Molecular Medicine and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Massinen
authors.forename: Marie-Estelle
authors.initials: ME
authors.lastname: Hokkanen
authors.forename: Hans
authors.initials: H
authors.lastname: Matsson
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tammimies
authors.forename: Isabel
authors.initials: I
authors.lastname: Tapia-Páez
authors.forename: Vanina
authors.initials: V
authors.lastname: Dahlström-Heuser
authors.forename: Juha
authors.initials: J
authors.lastname: Kuja-Panula
authors.forename: Jan
authors.initials: J
authors.lastname: Burghoorn
authors.forename: Kristian E
authors.initials: KE
authors.lastname: Jeppsson
authors.forename: Peter
authors.initials: P
authors.lastname: Swoboda
authors.forename: Myriam
authors.initials: M
authors.lastname: Peyrard-Janvid
authors.forename: Rune
authors.initials: R
authors.lastname: Toftgård
authors.forename: Eero
authors.initials: E
authors.lastname: Castrén
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D000089662:Doublecortin Protein; D020869:Gene Expression Profiling; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D051381:Rats; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C510451:DCDC2 protein, human; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D053823:Hedgehog Proteins; D008869:Microtubule-Associated Proteins