Pcdh11x, short for protocadherin 11 X-linked protein, is a cell adhesion molecule of the δ1-protocadherin family [4]. It has been implicated in multiple biological processes. In the nervous system, it is involved in circuit formation, and it may also play a role in pathways related to cell migration and invasion. Pcdh11x is of particular interest in understanding brain development and certain diseases [4]. Genetic models, such as KO mouse models, are valuable for studying its functions.

Using CRISPR/Cas9 genome editing to disrupt the Pcdh11x gene in mice, it was found that although mossy fiber (MF) sprouting in the adult hippocampus still developed, its target specificity was altered, with new synapses frequently formed on granule cell somata in addition to dendrites. This shows that Pcdh11x controls target specification of MF sprouting [1]. In cultured cortical neurons from embryonic day 16 mice, gain-of-function and loss-of-function experiments revealed that Pcdh11x negatively regulates dendritic branching. Overexpression of wild-type Pcdh11x reduced dendritic complexity, while knockdown of Pcdh11x increased dendritic branching, and it activates PI3K/AKT signaling to achieve this negative regulation [3].

In conclusion, Pcdh11x is crucial for proper nervous system development, regulating processes like dendritic branching and target specification of MF sprouting. The use of gene-knockout mouse models has been instrumental in uncovering these functions, which contribute to our understanding of brain development and related disorders. Additionally, Pcdh11x may have potential implications in cancer immunotherapy, as its mutation might serve as a specific biomarker to predict the efficacy of immune checkpoint inhibitors in lung adenocarcinoma patients [2].

References:

1. Luo, Wenshu, Cruz-Ochoa, Natalia Andrea, Seng, Charlotte, Lukacsovich, Tamás, Földy, Csaba. 2022. Pcdh11x controls target specification of mossy fiber sprouting. In Frontiers in neuroscience, 16, 888362. doi:10.3389/fnins.2022.888362. https://pubmed.ncbi.nlm.nih.gov/36117624/

2. Liu, Manjiao, Yang, Meijia, Zhang, Bei, Guo, Hao, Zhao, Jie. 2024. PCDH11X mutation as a potential biomarker for immune checkpoint therapies in lung adenocarcinoma. In Journal of molecular medicine (Berlin, Germany), 102, 899-912. doi:10.1007/s00109-024-02450-8. https://pubmed.ncbi.nlm.nih.gov/38739269/

3. Wu, Cuiying, Niu, Lijun, Yan, Zhongjie, Zhang, Peng, Xu, Ruxiang. 2015. Pcdh11x Negatively Regulates Dendritic Branching. In Journal of molecular neuroscience : MN, 56, 822-828. doi:10.1007/s12031-015-0515-8. https://pubmed.ncbi.nlm.nih.gov/25687328/

4. Priddle, Thomas H, Crow, Tim J. 2012. Protocadherin 11X/Y a human-specific gene pair: an immunohistochemical survey of fetal and adult brains. In Cerebral cortex (New York, N.Y. : 1991), 23, 1933-41. doi:10.1093/cercor/bhs181. https://pubmed.ncbi.nlm.nih.gov/22744706/