Increased expression of the dyslexia candidate gene DCDC2 affects length and signaling of primary cilia in neurons |
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Authors: | Massinen Satu Hokkanen Marie-Estelle Matsson Hans Tammimies Kristiina Tapia-Páez Isabel Dahlström-Heuser Vanina Kuja-Panula Juha Burghoorn Jan Jeppsson Kristian E Swoboda Peter Peyrard-Janvid Myriam Toftgård Rune Castrén Eero Kere Juha |
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Institution: | Research Program's Unit, Molecular Medicine and Department of Medical Genetics, University of Helsinki, Helsinki, Finland. |
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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. |
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