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 hydroce...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 Gprotein 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.展开更多
基金supported by grants from the China National Natural Science Foundation(82130052 and 81925017 to Tao Li,82001690 to Hong Cai)。
文摘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 Gprotein 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.
