A new study from the Yagi Group has been published in Communications Biology.
In this study, the authors demonstrate that protocadherin-γC4 is essential for suppressing neuronal cell death during development and for establishing dendritic self-avoidance in cerebellar Purkinje cells. They further show that introducing γC4 after birth can partially rescue the morphological abnormalities.
Although mutations in human PCDHGC4 are known to cause neurodevelopmental disorders, previously reported γC4-deficient mice die during the neonatal period, making it difficult to investigate the effects on postnatal brain development, neural circuit formation, and behavior.
In this work, the researchers established a new genome-editing strategy (the DOMINO method) that enables selective modification of γC4, allowing them to generate a new mouse model suitable for such analyses.
These findings are expected to accelerate the elucidation of pathogenic mechanisms underlying neurodevelopmental disorders, support the exploration of therapeutic strategies based on γC4 functional complementation, and contribute to research on related conditions such as autism spectrum disorder and schizophrenia, in which protocadherin dysfunction is implicated.
Congratulations!
Press Release : https://resou.osaka-u.ac.jp/ja/research/2026/20260326_2
Communications Biology : https://doi.org/10.1038/s42003-026-09778-6
