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Central microtubules (MTs), which are located in the lumen of ciliary axonemes, are non-centrosomal MTs that are crucial for motile cilia beating. However, the formation mechanism of central MTs remains elusive. Here, by using a Drosophila model, we identify Ccdc13 as a novel regulator for the assembly of central MTs. We show that Ccdc13 localizes along the central MTs and is essential for its formation in sperm flagella, with its deletion consequently affecting the sperm motility and the fertility of male flies. Mechanistically, we demonstrated that Ccdc13 directly interacts with Spef1, acting upstream of Spef1 to regulate central MT elongation. Remarkably, we demonstrated that the role of Ccdc13 in ciliary central MT formation is conserved in mammals. Ccdc13 deficiency in mice leads to the loss of central MTs in motile ependymal cilia, resulting in abnormal cilia motility and hydrocephalus. Our results mark the discovery of Ccdc13 as a novel regulator for ciliary central MT assembly and reveal that the Ccdc13\u2013Spef1 complex is an evolutionarily conserved module that is critical for central MT formation in motile cilia of both flies and mammals.<\/jats:p>","DOI":"10.1093\/nsr\/nwaf095","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T02:41:42Z","timestamp":1742265702000},"source":"Crossref","is-referenced-by-count":6,"title":["Ccdc13 is essential for the assembly of ciliary central microtubules"],"prefix":"10.1093","volume":"12","author":[{"given":"Zhimao","family":"Wu","sequence":"first","affiliation":[{"name":"School of Synthetic Biology, Shanxi Key Laboratory of Nucleic Acid Biopesticides, Shanxi University , Taiyuan 030006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences , Shanghai 200032 ,","place":["China"]},{"name":"Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS) , Shenzhen 518055 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences , Beijing 100039 ,","place":["China"]},{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences , Beijing 100039 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