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Abstract：
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.
摘要：
已显示含有卷曲螺旋结构域134（CCDC134）作为免疫细胞因子发挥抗肿瘤作用，并作为hADA2a的新型调节剂影响PCAF乙酰转移酶活性。虽然Ccdc134丢失会导致小鼠大脑发育异常，CCDC134在体内神经元发育中的意义存在争议。这里,我们报道,CCDC134在所有发育阶段的浦肯野细胞(PC)中高表达,并以细胞类型特异性方式调节哺乳动物小脑发育.小鼠神经干细胞（NSC）中Ccdc134的选择性缺失导致小脑形态发生缺陷，包括PC数量的减少和PC树突生长的损害，以及异常的颗粒细胞发育。此外，Ccdc134的丢失导致进行性运动功能障碍，运动协调和运动学习不足。最后,Ccdc134缺陷抑制了Wnt信号，但增加了Ataxin1水平。我们的发现提供了证据，证明CCDC134在小脑发育中起着重要作用。可能通过调节Wnt信号和Ataxin1表达水平，在控制小脑功能以进行运动协调和运动学习方面，最终使其成为小脑发病机制的潜在贡献者。
