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The Role of Bicaudal‐C in Kidney Development
Author(s) -
Wessely Oliver,
Agrawal Raman,
Tran Uyen
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.308.6
Subject(s) - nephron , biology , microbiology and biotechnology , kidney development , gene knockdown , xenopus , kidney , polycystic kidney disease , phenotype , rna binding protein , embryonic stem cell , messenger rna , gene , genetics
The RNA‐binding molecule Bicaudal‐C (BicC1) has been shown to regulate embryonic development in Drosophila and Xenopus . Interestingly, mouse mutants of Bicaudal‐C do not show early developmental defects, but develop polycystic kidney disease (PKD) instead. PKD is among the most common single gene diseases in humans and is the leading cause of end‐stage renal failure. It is characterized by the formation of fluid‐filled cysts in the kidney. Importantly, these cysts are thought to be caused by a defect in cell asymmetry causing kidney epithelial cells to misalign within the tubule leading to an increase of the tubule diameter. Here we provide data that BicC1 functions by regulating the expression of Polycystin‐2 (PC2), a member of the transient receptor potential super family. Knockout of BicC1 in mice results in the formation of early onset PKD characterized by cysts along the entire length of the nephron and reduced expression of PC2 in the kidney. Molecular analyses in Xenopus showed that BicC1 and PC2 cooperate and PC2 is required for the activity of BicC1. Moreover, at the subcellular level BicC1 protein was detected in cytoplasmic foci that were positive for P‐body markers such as GW182. Based on these data we propose that the PKD phenotype caused by loss‐of‐BicC1 in mice is caused by misregulation of of PC2 at the post‐transcriptional level.