Dysfunctional cilia lead to altered ependyma and choroid plexus function,and result in the formation of hydrocephalus
Abstract
Cilia are complex organelles involved in sensory perception and fluid or cell movement. They are constructed through a highly conserved process called intraflagellar transport (IFT). Mutations in IFT genes, such as Tg737, result in severe developmental defects and disease. In the case of the Tg737orpk mutants, these pathological alterations include cystic kidney disease, biliary and pancreatic duct abnormalities, skeletal patterning defects, and hydrocephalus. Here, we explore the connection between cilia dysfunction and the development of hydrocephalus by using the Tg737orpk mutants. Our analysis indicates that cilia on cells of the brain ventricles of Tg737orpk mutant mice are severely malformed. On the ependymal cells, these defects lead to disorganized beating and impaired cerebrospinal fluid (CSF) movement. However, the loss of the cilia beat and CSF flow is not the initiating factor, as the pathology is present prior to the development of motile cilia on these cells and CSF flow is not impaired at early stages of the disease. Rather, our results suggest that loss of cilia leads to altered function of the choroid plexus epithelum, as evidenced by elevated intracellular cAMP levels and increased chloride concentration in the CSF. These data suggest that cilia function is necessary for regulating ion transport and CSF production, as well as for CSF flow through the ventricles.
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Many of the genes in intraflagellar transport pathways are implicated in human diseases.
“Many of the genes in these pathways are implicated in human diseases [43].”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [43]
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Cites
Choroid Plexus in the Central Nervous System: Biology and Physiopathology
Strazielle, N., & Ghersi-Egea, J.-F. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.7.561 · Cited by 307 · see citing works
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- Britz, G. W., Kim, D. K. and Loeser, J. D. (1996). Hydrocephalus secondary to diffuse villous hyperplasia of the choroid plexus. Case report and review of the literature. J. Neurosurg. 85, 689-691.
- Bruni, J. E., Del Bigio, M. R. and Clattenburg, R. E. (1985). Ependyma: normal and pathological. A review of the literature. Brain Res. 356, 1-19.
- Ibraghimov-Beskrovnaya, O., Dackowski, W. R., Foggensteiner, L., Coleman, N., Thiru, S., Petry, L. R., Burn, T. C., Connors, T. D., Van Raay, T. et al. (1997). Polycystin: in vitro synthesis, in vivo tissue expression, and subcellular localization identifies a large membrane- associated protein. Proc. Natl. Acad. Sci. USA 94, 6397-6402.
- Olteanu, D., Yoder, B. K., Liu, W., Croyle, M. J., Welty, E. A., Rosborough, K., Wyss, J. M., Bell, P. D., Guay-Woodford, L. M., Bevensee, M. O. et al. (2005). Heightened ENaC-mediated sodium absorption in a murine polycystic kidney diease model epithelium lacking apical monocilia. Am. J. Physiol. Cell Physiol. (in press).
- W. G. Bradley, R. B. Daroff, G. M. Fenichel and C. D. Marsden), pp. 521-595. Woburn, MA: Butterworth-Heinemann.
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- Authors
- Banizs, B., Pike, M. M., Millican, C. L., Ferguson, W. B., Komlosi, P., Sheetz, J., Bell, P. D., Schwiebert, E. M., & Yoder, B. K.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2005-12-01
- Volume
- 132
- Issue
- 23
- Pages
- 5329-5339
- ISSN
- 1477-9129
- 0950-1991
- Cited by
- 349
- References
- 1
- Language
- en
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