|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online June 28, 2004
doi: 10.1242/10.1242/dev.01189
1 Diabetes Center, Department of Medicine, University of California, San
Francisco, CA 94143, USA
2 Department of Pediatrics, Case Western Reserve University, Cleveland, OH
44106, USA
3 Program in Molecular Medicine, University of Massachusetts Medical School,
Worcester, MA 01605, USA
* Author for correspondence (e-mail: mhebrok{at}diabetes.ucsf.edu)
Accepted 29 March 2004
Polycystic kidney disease (PKD) includes a group of disorders that are characterized by the presence of cysts in the kidney and other organs, including the pancreas. Here we show that in orpk mice, a model system for PKD that harbors a mutation in the gene that encodes the polaris protein, pancreatic defects start to occur at the end of gestation, with an initial expansion of the developing pancreatic ducts. Ductal dilation continues rapidly after birth and results in the formation of large, interconnected cysts. Expansion of pancreatic ducts is accompanied by apoptosis of neighboring acinar cells, whereas endocrine cell differentiation and islet formation appears to be unaffected. Polaris has been shown to co-localize with primary cilia, and these structures have been implicated in the formation of renal cysts. In the orpk pancreas, cilia numbers are reduced and cilia length is decreased. Expression of polycystin-2, a protein involved in PKD, is mislocalized in orpk mice. Furthermore, the cellular localization of ß-catenin, a protein involved in cell adhesion and Wnt signaling, is altered. Thus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas.
Key words: Pancreas, Cilia, Polycystic kidney disease, Polaris, orpk, Acinar-ductal metaplasia, Wnt signaling
This article has been cited by other articles:
|
|
 |
|
  A.-R. Gallagher, E. L. Esquivel, T. S. Briere, X. Tian, M. Mitobe, L. F. Menezes, G. S. Markowitz, D. Jain, L. F. Onuchic, and S. Somlo Biliary and Pancreatic Dysgenesis in Mice Harboring a Mutation in Pkhd1 Am. J. Pathol., February 1, 2008; 172(2): 417 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Yoder Role of Primary Cilia in the Pathogenesis of Polycystic Kidney Disease J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1381 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ait-Lounis, D. Baas, E. Barras, C. Benadiba, A. Charollais, R. Nlend Nlend, D. Liegeois, P. Meda, B. Durand, and W. Reith Novel Function of the Ciliogenic Transcription Factor RFX3 in Development of the Endocrine Pancreas Diabetes, April 1, 2007; 56(4): 950 - 959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Banizs, P. Komlosi, M. O. Bevensee, E. M. Schwiebert, P. D. Bell, and B. K. Yoder Altered pHi regulation and Na+/HCO3- transporter activity in choroid plexus of cilia-defective Tg737orpk mutant mouse Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1409 - C1416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Haycraft, Q. Zhang, B. Song, W. S. Jackson, P. J. Detloff, R. Serra, and B. K. Yoder Intraflagellar transport is essential for endochondral bone formation Development, January 15, 2007; 134(2): 307 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Bisgrove and H. J. Yost The roles of cilia in developmental disorders and disease Development, November 1, 2006; 133(21): 4131 - 4143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Peruzzi, G. Athauda, and D. P. Bottaro The von Hippel-Lindau tumor suppressor gene product represses oncogenic beta-catenin signaling in renal carcinoma cells PNAS, September 26, 2006; 103(39): 14531 - 14536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Arsov, D. G. Silva, M. K. O'Bryan, A. Sainsbury, N. J. Lee, C. Kennedy, S. S.M. Manji, K. Nelms, C. Liu, C. G. Vinuesa, et al. Fat Aussie--A New Alstrom Syndrome Mouse Showing a Critical Role for ALMS1 in Obesity, Diabetes, and Spermatogenesis Mol. Endocrinol., July 1, 2006; 20(7): 1610 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Banizs, M. M. Pike, C. L. Millican, W. B. Ferguson, P. Komlosi, J. Sheetz, P. D. Bell, E. M. Schwiebert, and B. K. Yoder Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus Development, December 1, 2005; 132(23): 5329 - 5339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Davenport and B. K. Yoder An incredible decade for the primary cilium: a look at a once-forgotten organelle Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1159 - F1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Kramer-Zucker, F. Olale, C. J. Haycraft, B. K. Yoder, A. F. Schier, and I. A. Drummond Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis Development, April 15, 2005; 132(8): 1907 - 1921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Pazour Intraflagellar Transport and Cilia-Dependent Renal Disease: The Ciliary Hypothesis of Polycystic Kidney Disease J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2528 - 2536. [Abstract] [Full Text] [PDF]
|
|
