Ccdc134 deficiency impairs cerebellar development and motor coordination,Genes, Brain and Behavior

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Ccdc134 deficiency impairs cerebellar development and motor coordination
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2021-08-12 , DOI: 10.1111/gbb.12763
Sha Yin _{1,

2} , Qinyuan Liao ₃ , Yida Wang _{1,

2} , Qianwen Shi _{1,

2} , Peng Xia _{1,

2} , Ming Yi ₄ , Jing Huang _{1,

2}

Affiliation

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.

中文翻译：

Ccdc134 缺乏会损害小脑发育和运动协调

含有 134 (CCDC134) 的卷曲螺旋结构域已被证明可作为免疫细胞因子发挥抗肿瘤作用，并作为 hADA2a 的新型调节剂来影响 PCAF 乙酰转移酶活性。虽然Ccdc134缺失会导致小鼠大脑发育异常，但 CCDC134 在体内神经元发育中的意义仍存在争议。在这里，我们报道 CCDC134 在所有发育阶段的浦肯野细胞 (PC) 中高度表达，并以细胞类型特异性的方式调节哺乳动物小脑的发育。小鼠神经干细胞 (NSC) 中Ccdc134的选择性缺失会导致小脑形态发生缺陷，包括 PC 数量减少、PC 树突生长受损以及颗粒细胞发育异常。此外， Ccdc134的缺失会导致进行性运动功能障碍，导致运动协调和运动学习缺陷。最后， Ccdc134缺陷抑制 Wnt 信号传导，但增加 Ataxin1 水平。我们的研究结果证明 CCDC134 在小脑发育中发挥重要作用，可能是通过调节 Wnt 信号传导和 Ataxin1 表达水平，以及控制小脑运动协调和运动学习功能，最终使其成为小脑发病机制的潜在贡献者。

更新日期：2021-09-14

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