Loss of Rsph9 causes neonatal hydrocephalus with abnormal development of motile cilia in mice
Open Access
- 23 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-11
- https://doi.org/10.1038/s41598-020-69447-4
Abstract
Hydrocephalus is a brain disorder triggered by cerebrospinal fluid accumulation in brain cavities. Even though cerebrospinal fluid flow is known to be driven by the orchestrated beating of the bundled motile cilia of ependymal cells, little is known about the mechanism of ciliary motility. RSPH9 is increasingly becoming recognized as a vital component of radial spokes in ciliary "9 + 2" ultrastructure organization. Here, we show that deletion of the Rsph9 gene leads to the development of hydrocephalus in the early postnatal period. However, the neurodevelopment and astrocyte development are normal in embryonic Rsph9(-/-) mice. The tubular structure of the central aqueduct was comparable in Rsph9(-/-) mice. Using high-speed video microscopy, we visualized lower beating amplitude and irregular rotation beating pattern of cilia bundles in Rsph9(-/-) mice compared with that of wild-type mice. And the centriolar patch size was significantly increased in Rsph9(-/-) cells. TEM results showed that deletion of Rsph9 causes little impact in ciliary axonemal organization but the Rsph9(-/-) cilia frequently had abnormal ectopic ciliary membrane inclusions. In addition, hydrocephalus in Rsph9(-/-) mice results in the development of astrogliosis, microgliosis and cerebrovascular abnormalities. Eventually, the ependymal cells sloughed off of the lateral wall. Our results collectively suggested that RSPH9 is essential for ciliary structure and motility of mouse ependymal cilia, and its deletion causes the pathogenesis of hydrocephalus.Funding Information
- CAS Strategic Priority Research Program (XDA16010301)
- National Key R&D Program of China (2019YFA0110300, 2018YFA0108402)
- K.C.Wong Education Foundation
This publication has 36 references indexed in Scilit:
- CNS sterile injury: just another wound healing?Trends in Molecular Medicine, 2013
- Analysis of ependymal ciliary beat pattern and beat frequency using high speed imaging: comparison with the photomultiplier and photodiode methodsCilia, 2012
- Subunit interactions within the Chlamydomonas flagellar spokeheadCytoskeleton, 2011
- Reactive astrocytosis, microgliosis and inflammation in rats with neonatal hydrocephalusExperimental Neurology, 2010
- Congenital hydrocephalus – prevalence, prenatal diagnosis and outcome of pregnancy in four European regionsEuropean Journal of Paediatric Neurology, 2010
- Inflammasome signaling at the heart of central nervous system pathologyJournal of Neuroscience Research, 2010
- Mutations in Radial Spoke Head Protein Genes RSPH9 and RSPH4A Cause Primary Ciliary Dyskinesia with Central-Microtubular-Pair AbnormalitiesAmerican Journal of Human Genetics, 2009
- Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in experimental hydrocephalusFluids and Barriers of the CNS, 2007
- Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleusNature, 2002
- Regulation of Daily Locomotor Activity and Sleep by Hypothalamic EGF Receptor SignalingScience, 2001