Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus

Boglarka Banizs, Martin Pike, C. Leigh Millican, William B. Ferguson, Peter Komlosi, James Sheetz, Phillip D. Bell, Erik M. Schwiebert, Bradley K. Yoder

Research output: Contribution to journalArticle

213 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5329-5339
Number of pages11
JournalDevelopment
Volume132
Issue number23
DOIs
StatePublished - Dec 2005
Externally publishedYes

Fingerprint

Ependyma
Choroid Plexus
Cilia
Hydrocephalus
Cerebrospinal Fluid
Cystic Kidney Diseases
Pancreatic Ducts
Ion Transport
Organelles
Cell Movement
Chlorides
Pathology
Mutation
Brain

Keywords

  • Choroid plexus
  • Cilia
  • Ependyma
  • Hydrocephalus
  • Intraflagellar transport
  • Tg737

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Banizs, B., Pike, M., Millican, C. L., Ferguson, W. B., Komlosi, P., Sheetz, J., ... Yoder, B. K. (2005). Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development, 132(23), 5329-5339. https://doi.org/10.1242/dev.02153

Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. / Banizs, Boglarka; Pike, Martin; Millican, C. Leigh; Ferguson, William B.; Komlosi, Peter; Sheetz, James; Bell, Phillip D.; Schwiebert, Erik M.; Yoder, Bradley K.

In: Development, Vol. 132, No. 23, 12.2005, p. 5329-5339.

Research output: Contribution to journalArticle

Banizs, B, Pike, M, Millican, CL, Ferguson, WB, Komlosi, P, Sheetz, J, Bell, PD, Schwiebert, EM & Yoder, BK 2005, 'Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus', Development, vol. 132, no. 23, pp. 5329-5339. https://doi.org/10.1242/dev.02153
Banizs, Boglarka ; Pike, Martin ; Millican, C. Leigh ; Ferguson, William B. ; Komlosi, Peter ; Sheetz, James ; Bell, Phillip D. ; Schwiebert, Erik M. ; Yoder, Bradley K. / Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. In: Development. 2005 ; Vol. 132, No. 23. pp. 5329-5339.
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