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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:p>\n                    Defects in multiciliated ependymal cells (ECs), which line the cerebral ventricular walls and generate unidirectional cerebrospinal fluid (CSF) flow through coordinated ciliary beating, can lead to CSF accumulation and hydrocephalus.\n                    <jats:italic toggle=\"yes\">TMEM216<\/jats:italic>\n                    , a ciliopathy-associated gene mutated in Joubert, Meckel, and related syndromes, encodes an essential component of the protein complexes that form the transition zone (TZ) at the base of primary cilia. Here, we demonstrate that central nervous system-specific inactivation of\n                    <jats:italic toggle=\"yes\">Tmem216<\/jats:italic>\n                    results in severe postnatal hydrocephalus. TMEM216 localizes to the TZ of motile cilia in ECs and the TZ of primary cilia in radial glia cells (RGCs), the embryonic precursors of ECs. While\n                    <jats:italic toggle=\"yes\">Tmem216<\/jats:italic>\n                    -deficient ECs differentiate normally, TZ structure and ciliogenesis in both ECs and RGCs are severely disrupted, as shown by reduced cilia abundance and disrupted ciliary ultrastructure. These defective cilia exhibit immobility or dyskinetic movement, resulting in significantly slower CSF flow in\n                    <jats:italic toggle=\"yes\">Tmem216<\/jats:italic>\n                    mutants than controls. In addition to aberrant ciliogenesis and ciliary dysfunction,\n                    <jats:italic toggle=\"yes\">Tmem216<\/jats:italic>\n                    ablation disrupts both translational polarity (asymmetric positioning of cilia on the apical area) in RGCs and ECs, as well as rotational polarity (unidirectional orientation of basal bodies within individual ECs and intercellular rotational alignment of motile cilia) in ECs. These findings identify TMEM216 as a critical TZ protein essential for ciliogenesis during ependymal development and establishing ependymal planar cell polarity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2615477123","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:02:15Z","timestamp":1789059735000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["<i>Tmem216<\/i>\n                    deficiency induces hydrocephalus via impaired ciliogenesis and disrupted ependymal planar polarity in mice"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5226-1044","authenticated-orcid":false,"given":"Qianqian","family":"Gong","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Shandong Provincial Key Laboratory of Development and Regeneration, School of Life Sciences, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuowen","family":"Lv","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Shandong Provincial Key Laboratory of Development and Regeneration, School of Life Sciences, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Dou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Shandong Provincial Key Laboratory of Development and Regeneration, School of Life Sciences, Shandong University","place":["Qingdao, China"]},{"name":"Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University","place":["Jinan, 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