{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:23:20Z","timestamp":1791570200891,"version":"4.3.4"},"reference-count":41,"publisher":"The Company of Biologists","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,12,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1242\/dev.02153","type":"journal-article","created":{"date-parts":[[2005,11,10]],"date-time":"2005-11-10T22:38:12Z","timestamp":1131662292000},"page":"5329-5339","source":"Crossref","is-referenced-by-count":348,"title":["Dysfunctional cilia lead to altered ependyma and choroid plexus function,and result in the formation of hydrocephalus"],"prefix":"10.1242","volume":"132","author":[{"given":"Boglarka","family":"Banizs","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Alabama at Birmingham, Birmingham,AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M.","family":"Pike","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Leigh","family":"Millican","sequence":"additional","affiliation":[{"name":"High Resolution Imaging Facility, University of Alabama at Birmingham,Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Komlosi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Nephrology Research and Training Center, University of Alabama at Birmingham,Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Sheetz","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Alabama at Birmingham, Birmingham,AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip D.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Nephrology Research and Training Center, University of Alabama at Birmingham,Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik M.","family":"Schwiebert","sequence":"additional","affiliation":[{"name":"Nephrology Research and Training Center, University of Alabama at Birmingham,Birmingham, AL 35294, USA"},{"name":"Department of Physiology and Biophysics, University of Alabama at Birmingham,Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley K.","family":"Yoder","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Alabama at Birmingham, Birmingham,AL 35294, USA"},{"name":"Nephrology Research and Training Center, University of Alabama at Birmingham,Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042605280764500_REF1","doi-asserted-by":"crossref","unstructured":"Avner, E. 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O., Kida, S. and Zhang, E. T.(1992). Pathways of fluid drainage from the brain \u2013morphological aspects and immunological significance in rat and man. Brain Pathol.2,277-284.","DOI":"10.1111\/j.1750-3639.1992.tb00704.x"},{"key":"2021042605280764500_REF37","doi-asserted-by":"crossref","unstructured":"Wilson, P. D. (1997). Epithelial cell polarity and disease. Am. J. Physiol.272,F434-F442.","DOI":"10.1152\/ajprenal.1997.272.4.F434"},{"key":"2021042605280764500_REF38","unstructured":"Yoder, B. K., Richards, W. G., Sommardahl, C., Sweeney, W. E.,Michaud, E. J., Wilkinson, J. E., Avner, E. D. and Woychik, R. P.(1997). Differential rescue of the renal and hepatic disease in an autosomal recessive polycystic kidney disease mouse mutant. A new model to study the liver lesion. Am. J. Pathol.150,2231-2241."},{"key":"2021042605280764500_REF39","unstructured":"Yoder, B. K., Tousson, A., Millican, L., Wu, J. H., Bugg, C. E.,Jr, Schafer, J. A. and Balkovetz, D. F. (2002). Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium. Am. J. Physiol. Renal Physiol.282,F541-F552."},{"key":"2021042605280764500_REF40","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Murcia, N. S., Chittenden, L. R., Richards, W. G.,Michaud, E. J., Woychik, R. P. and Yoder, B. K. (2003). Loss of the Tg737 protein results in skeletal patterning defects. Dev. Dyn.227,78-90.","DOI":"10.1002\/dvdy.10289"},{"key":"2021042605280764500_REF41","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Davenport, J. R., Croyle, M. J., Haycraft, C. J. and Yoder, B. K. (2005). Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737(orpk) mutant mice. Lab. 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