Journal
DEVELOPMENT
Volume 131, Issue 14, Pages 3457-3467Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.01189
Keywords
pancreas; cilia; polycystic kidney disease; polaris; orpk; acinar-ductal metaplasia; Wnt signaling
Categories
Funding
- NIDDK NIH HHS [DK61245-01, U19 DK061245, DK57306-05] Funding Source: Medline
- NIGMS NIH HHS [GM-60992] Funding Source: Medline
Ask authors/readers for more resources
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 beta-catenin, a protein involved in cell adhesion and Writ signaling, is altered. Thus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available