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Our previous work demonstrated critical roles of atypical cadherin Celsr2 during neural development, including cilia organization, neuron migration and axon navigation. Here, we address its role in axon regeneration.<\/jats:p>\n               <jats:p>We show that Celsr2 is highly expressed in both mouse and human spinal motor neurons. Celsr2 knockout promotes axon regeneration and fasciculation in mouse cultured spinal explants. Similarly, cultured Celsr2 mutant motor neurons extend longer neurites and larger growth cones, with increased expression of end-binding protein 3 and higher potassium-induced calcium influx. Mice with Celsr2 conditional knockout in spinal motor neurons do not exhibit any behavioural deficits; however, after branchial plexus injury, axon regeneration and functional forelimb locomotor recovery are significantly improved. Similarly, knockdown of CELSR2 using shRNA interference in cultured human spinal motor explants and motor neurons increases axonal fasciculation and growth. In mouse adult spinal cord after root avulsion, in mouse embryonic spinal cords, and in cultured human motor neurons, Celsr2 downregulation is accompanied by increased levels of GTP-bound Rac1 and Cdc42, and of JNK and c-Jun.<\/jats:p>\n               <jats:p>In conclusion, Celsr2 negatively regulates motor axon regeneration and is a potential target to improve neural repair.<\/jats:p>","DOI":"10.1093\/brain\/awab317","type":"journal-article","created":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T13:05:49Z","timestamp":1629551149000},"page":"670-683","source":"Crossref","is-referenced-by-count":26,"title":["Inactivating <i>Celsr2<\/i> promotes motor axon fasciculation and regeneration in mouse and human"],"prefix":"10.1093","volume":"145","author":[{"given":"Quan","family":"Wen","sequence":"first","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huandi","family":"Weng","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingtai","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, P. R. China"},{"name":"University of Chinese Academy of Sciences, Beijing 100101, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadel","family":"Tissir","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Developmental Neurobiology, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Qu","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, P. R. China"},{"name":"Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain- Inspired Intelligence, Guangzhou 510515, P. R. China"},{"name":"Co-innovation Center of Neuroregeneration, Nantong University, Jiangsu, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8975-5228","authenticated-orcid":false,"given":"Libing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, P. R. China"},{"name":"Co-innovation Center of Neuroregeneration, Nantong University, Jiangsu, P. R. China"},{"name":"Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, P. R. China"},{"name":"Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, Guangzhou 510632, P. R. 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