The canonical Wnt signaling pathway is not involved in renal cyst development in the kidneys of inv mutant mice.
Recent studies have identified several genes whose defects cause hereditary renal cystic diseases with most of the gene products located in the primary cilia. It has been suggested that primary cilia are involved in signaling pathways, defects of which result in abnormal cell proliferation and randomization of oriented cell division in the kidney leading to cyst formation. Mice with a mutation in the inv gene are a model for human nephronophthisis type 2 and develop multiple renal cysts. Inv protein (also called inversin) is located in the base of primary cilia and acts as a switch from canonical to non-canonical Wnt signaling. Here, we studied the orientation of cell division and proliferation in the kidneys of inv mutant mice, as its loss is thought to maintain activation of the canonical Wnt signaling. To establish if canonical signaling was involved in this process, we mated inv mutant with BATlacZ mice to measure canonical Wnt activity. Based on these reporter mice, nuclear localization and phosphorylation of β-catenin, and responsiveness to Wnt ligands in inv mutant cells, we found that random oriented cell division is an initial event for renal tubule expansion and precedes cell proliferation. Thus, our results do not support the hypothesis that canonical Wnt signaling causes renal cyst development in these mice.
Department of Anatomy and Developmental Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Noriyuki
N
Sugiyama
Tadasuke
T
Tsukiyama
Terry P
TP
Yamaguchi
Takahiko
T
Yokoyama
D000818:Animals; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D007668:Kidney / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000209:etiology*; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D008941:Spindle Apparatus / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology
C495267:CTNNB1 protein, mouse; C491947:Invs protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D048049:Extracellular Signal-Regulated MAP Kinases
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