| Title | Ccdc134 deficiency impairs cerebellar development and motor coordination |
| Authors | Yin, Sha Liao, Qinyuan Wang, Yida Shi, Qianwen Xia, Peng Yi, Ming Huang, Jing |
| Affiliation | Peking Univ, Dept Immunol, Sch Basic Med Sci, 38 Xueyuan Rd, Beijing, Peoples R China Peking Univ, NHC Key Lab Med Immunol, Beijing, Peoples R China Chinese Acad Med Sci, Key Lab Mol Immunol, Beijing, Peoples R China Guilin Med Univ, Dept Immunol, Guilin, Guangxi Provinc, Peoples R China Peking Univ, Neurosci Res Inst, Beijing, Peoples R China Peking Univ, Key Lab Neurosci, Minist Educ, Natl Hlth Commiss China, Beijing, Peoples R China |
| Keywords | MICE EXPRESSING F3/CONTACTIN CELL-MIGRATION NERVOUS-SYSTEM PROTEIN DIFFERENTIATION GENE SIX3 HAPLOINSUFFICIENCY NEUROGENESIS ACTIVATION |
| Issue Date | Aug-2021 |
| Publisher | GENES BRAIN AND BEHAVIOR |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/623818 |
| ISSN | 1601-1848 |
| DOI | 10.1111/gbb.12763 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 |
