Ccdc134 deficiency impairs cerebellar development and motor coordination

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Coiled-coil domain containing 134 (CCDC134) has known roles in immunity and acetyltransferase activity.
• Its specific function in in vivo neuronal development remains controversial.
• CCDC134 is notably expressed in Purkinje cells (PCs) throughout development.

Purpose of the Study:

• To investigate the role of CCDC134 in mammalian cerebellar development and function.
• To elucidate the cell-type-specific effects of CCDC134 during cerebellar development.

Main Methods:

• Selective deletion of Ccdc134 in mouse neural stem cells (NSCs).
• Analysis of cerebellar development, including Purkinje cell (PC) number and dendritic growth.
• Assessment of motor function, coordination, and learning in mice.
• Investigation of Wnt signaling pathway and Ataxin1 expression levels.

Main Results:

• Selective Ccdc134 deletion in NSCs impaired cerebellar morphogenesis, reducing PC numbers and dendritic growth.
• Granule cell development was also abnormal in Ccdc134-deficient mice.
• Mice lacking Ccdc134 exhibited progressive motor dysfunction, including impaired motor coordination and learning.
• CCDC134 deficiency was associated with inhibited Wnt signaling and increased Ataxin1 levels.

Conclusions:

• CCDC134 plays a critical cell-type-specific role in mammalian cerebellar development.
• CCDC134 is essential for maintaining normal motor coordination and motor learning.
• The findings suggest CCDC134 regulates cerebellar function via Wnt signaling and Ataxin1, potentially contributing to cerebellar pathogenesis.