2. Academic Validation
  3. RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus

RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus

  • Sci China Life Sci. 2024 Oct 10. doi: 10.1007/s11427-024-2720-8.
Xue Pang # 1,  Lin Gu # 1,  Qiu-Ying Han 1,  Jia-Qing Xing 1,  Ming Zhao 1,  Shao-Yi Huang 1,  Jun-Xi Yi 1,  Jie Pan 1,  Hao Hong 1,  Wen Xue 1,  Xue-Qing Zhou 1,  Zhi-Hui Su 1,  Xin-Ran Zhang 1,  Li-Ming Sun 1,  Shao-Zhen Jiang 1 2,  Dan Luo 1 3,  Ling Chen 1 3,  Zheng-Jie Wang 1,  Yu Yu 1,  Tian Xia 1,  Xue-Min Zhang 1 2 3,  Ai-Ling Li 1 2,  Tao Zhou 1,  Hong Cai 4,  Tao Li 5 6 7
Affiliations

Affiliations

  • 1 Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, 100039, China.
  • 2 School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
  • 3 Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China.
  • 4 Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, 100039, China. hcai@xmail.ncba.ac.cn.
  • 5 Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, 100039, China. tli@ncba.ac.cn.
  • 6 School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. tli@ncba.ac.cn.
  • 7 Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China. tli@ncba.ac.cn.
  • # Contributed equally.
PMID: 39400871 DOI: 10.1007/s11427-024-2720-8
Abstract

Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid (CSF) flow by beating their motile cilia coordinately. The ependymal denudation or ciliary dysfunction causes hydrocephalus. Here, we report that the deficiency of regulator of G-protein signaling 22 (RGS22) results in severe congenital hydrocephalus in both mice and rats. Interestingly, RGS22 is specifically expressed in ependymal cells within the brain. Using conditional knock-out mice, we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus. Mechanistically, we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis. This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor (LPAR) signaling under Rgs22-/- condition, as the LPAR blockade effectively alleviates hydrocephalus in Rgs22-/- rats. Therefore, our findings unveil a previously unrecognized role of RGS22 in the central nervous system, and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.

Keywords

RGS22; ependymal cells; hydrocephalus.

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