CELSR1, short for cadherin EGF LAG seven-pass G-type receptor 1, is an adhesion G protein-coupled receptor (aGPCR) [2]. It plays crucial roles in neurodevelopment, epithelial planar cell polarity (PCP), and is involved in pathways like Wnt/PCP [3,5,6]. It has been shown to be important for normal development of the nervous system and epithelium, and its dysfunction may lead to various diseases [1,3,5]. Genetic models, such as KO/CKO mouse models, are valuable in studying its functions.

In KO mouse models, loss of Celsr1 leads to incorrect rostral migration of facial branchiomotor neurons, indicating its role in suppressing Wnt5a-mediated chemoattraction during hindbrain development [6]. In addition, removal of Celsr1 function alone abolishes PCP protein asymmetry and hair follicle polarization in the skin, highlighting its major role in epidermal PCP establishment [7].

In conclusion, CELSR1 is essential for multiple biological processes including neuronal migration and epidermal PCP. Studies using KO/CKO mouse models have revealed its significance in these processes, and also implicated its role in diseases such as partial epilepsy of childhood, glioma, ovarian cancer, and congenital heart diseases like familial bicuspid aortic valve and hypoplastic left heart syndrome [1,4,8,9].

References:

1. Chen, Zheng, Luo, Sheng, Liu, Zhi-Gang, Bian, Wen-Jun, Liao, Wei-Ping. 2022. CELSR1 variants are associated with partial epilepsy of childhood. In American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 189, 247-256. doi:10.1002/ajmg.b.32916. https://pubmed.ncbi.nlm.nih.gov/36453712/

2. Bui, Duy Lan Huong, Roach, Andrew, Li, Jingxian, Araç, Demet, Sando, Richard C. 2023. The adhesion GPCRs CELSR1-3 and LPHN3 engage G proteins via distinct activation mechanisms. In Cell reports, 42, 112552. doi:10.1016/j.celrep.2023.112552. https://pubmed.ncbi.nlm.nih.gov/37224017/

3. Goffinet, Andre M, Tissir, Fadel. 2017. Seven pass Cadherins CELSR1-3. In Seminars in cell & developmental biology, 69, 102-110. doi:10.1016/j.semcdb.2017.07.014. https://pubmed.ncbi.nlm.nih.gov/28716607/

4. Wang, Guang, Li, Yong, Zhang, Dongxia, Sun, Xiaochuan, Zhang, Bingqian. 2020. CELSR1 Acts as an Oncogene Regulated by miR-199a-5p in Glioma. In Cancer management and research, 12, 8857-8865. doi:10.2147/CMAR.S258835. https://pubmed.ncbi.nlm.nih.gov/33061581/

5. Boutin, Camille, Goffinet, André M, Tissir, Fadel. . Celsr1-3 cadherins in PCP and brain development. In Current topics in developmental biology, 101, 161-83. doi:10.1016/B978-0-12-394592-1.00010-7. https://pubmed.ncbi.nlm.nih.gov/23140629/

6. Hummel, Devynn, Becks, Alexandria, Men, Hongsheng, Glasco, Derrick M, Chandrasekhar, Anand. 2022. Celsr1 suppresses Wnt5a-mediated chemoattraction to prevent incorrect rostral migration of facial branchiomotor neurons. In Development (Cambridge, England), 149, . doi:10.1242/dev.200553. https://pubmed.ncbi.nlm.nih.gov/36325991/

7. Basta, Lena P, Sil, Parijat, Jones, Rebecca A, Hayward-Lara, Gabriela, Devenport, Danelle. 2023. Celsr1 and Celsr2 exhibit distinct adhesive interactions and contributions to planar cell polarity. In Frontiers in cell and developmental biology, 10, 1064907. doi:10.3389/fcell.2022.1064907. https://pubmed.ncbi.nlm.nih.gov/36712970/

8. Theis, Jeanne L, Niaz, Talha, Sundsbak, Rhianna S, Hagler, Donald J, Olson, Timothy M. 2022. CELSR1 Risk Alleles in Familial Bicuspid Aortic Valve and Hypoplastic Left Heart Syndrome. In Circulation. Genomic and precision medicine, 15, e003523. doi:10.1161/CIRCGEN.121.003523. https://pubmed.ncbi.nlm.nih.gov/35133174/

9. Zuo, Jiwei, Zheng, Anqi, Wang, Xingyue, Tang, Kai-Fu, Du, Xing. 2023. Upregulation of CELSR1 expression promotes ovarian cancer cell proliferation, migration, and invasion. In Medical oncology (Northwood, London, England), 41, 10. doi:10.1007/s12032-023-02232-1. https://pubmed.ncbi.nlm.nih.gov/38070011/