Ccdc134 deficiency impairs cerebellar development and motor coordination.

Coiled-coil domain containing 134 (CCDC134) has been shown to serve as an immune cytokine to exert antitumor effects and to act as a novel regulator of hADA2a to affect PCAF acetyltransferase activity. While Ccdc134 loss causes abnormal brain development in mice, the significance of CCDC134 in neuronal development in vivo is controversial. Here, we report that CCDC134 is highly expressed in Purkinje cells (PCs) at all developmental stages and regulates mammalian cerebellar development in a cell type-specific manner. Selective deletion of Ccdc134 in mouse neural stem cells (NSCs) caused defects in cerebellar morphogenesis, including a decrease in the number of PCs and impairment of PC dendritic growth, as well as abnormal granule cell development. Moreover, loss of Ccdc134 caused progressive motor dysfunction with deficits in motor coordination and motor learning. Finally, Ccdc134 deficiency inhibited Wnt signaling but increased Ataxin1 levels. Our findings provide evidence that CCDC134 plays an important role in cerebellar development, possibly through regulating Wnt signaling and Ataxin1 expression levels, and in controlling cerebellar function for motor coordination and motor learning, ultimately making it a potential contributor to cerebellar pathogenesis.