Increased expression of the dyslexia candidate gene DCDC2 affects length and signaling of primary cilia in neurons

阅读障碍候选基因 DCDC2 表达增加会影响神经元初级纤毛的长度和信号传导

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作者:Satu Massinen, Marie-Estelle Hokkanen, Hans Matsson, Kristiina Tammimies, Isabel Tapia-Páez, Vanina Dahlström-Heuser, Juha Kuja-Panula, Jan Burghoorn, Kristian E Jeppsson, Peter Swoboda, Myriam Peyrard-Janvid, Rune Toftgård, Eero Castrén, Juha Kere

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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