Tmem216 deficiency induces hydrocephalus via impaired ciliogenesis and disrupted ependymal planar polarity in mice

Title of Paper:Tmem216 deficiency induces hydrocephalus via impaired ciliogenesis and disrupted ependymal planar polarity in mice

Journal:PNAS

Summary: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. TMEM216, 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 Tmem216 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 Tmem216-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 Tmem216 mutants than controls. In addition to aberrant ciliogenesis and ciliary dysfunction, Tmem216 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.

First Author:Gong Qianqian

Correspondence Author:Shao Ming,Su Ling,Liu Xiangguo,Sun Xiaoyang

All the Authors:Lv Zhuowen,Dou Zhilin,Wang Sen,Zhang Keyi,Guo Yuyu,Wang yingying

Indexed by:Journal paper

Discipline:Natural Science

First-Level Discipline:Biology

Translation or Not:No

Date of Publication:2026-09

Included Journals:SCI

Release Time:2026-09-11