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Differentiation is the process by which tissues/organs take on their final, physiologically functional form. This process is mediated in part by the silencing of embryonic genes and the activation of terminal, differentiation gene products. Mammalian kidney development is initiated when the Wolffian duct branches and invades the overlying metanephric mesenchyme. The newly formed epithelial bud, known as the ureteric bud, will continue to branch ultimately differentiating into the collecting duct system and ureter. Here, we show that Hoxb7-Cre mediated removal of beta-catenin from the mouse Wolffian ductepithelium leads to the premature expression of gene products normally associated with the differentiated kidneycollecting duct system including the water channel protein, Aquaporin-3 and the tight junction protein isoform, ZO-1 alpha+. Mutant cells fail to maintain expression of some genes associated with embryonic development, including several mediators of branching morphogenesis, which subsequently leads to kidney aplasia or hypoplasia. Reciprocally, expression of a stabilized form of beta-catenin appears to block differentiation of the collecting ducts. All of these defects occur in the absence of any effects on the adherens junctions. These data indicate a role for beta-catenin in maintaining cells of the Wolffian ducts and the duct derived ureteric bud/collecting duct system in an undifferentiated or precursor state.
Fig. 1. Sagittal sections through e11.5 β-catenin mutant Wolffian ducts. β-Catenin staining shows that extruded epithelia can be either wildtype (A) or mutant (B). Ducts have been double stained with antibodies for Pax-2 (single channel red in panels A′ and B′) and β-catenin (single channel green in panels A and B). Arrows indicate ectopic epithelia.
Fig. 2. Development of the Wolffian duct and ureteric bud at e11.5 and e12.5. Lac-Z stained e11.5 (A, C, E) and e12.5 (B, D, F) Hoxb7-Cre; β-catenin+/c; ROSA+/− (wildtype, A and B) and Hoxb7-Cre; β-catenin−/c;ROSA+/− (mutant, C–F) urogenital systems. Hoxb7-Cre is active in the Wolffian duct (red arrows) and ureteric bud (black arrows) of e11.5–12.5 urogenital systems (A and B). β-Catenin mutant collecting ducts show multiple ectopic bud structures branching from the Wolffian duct (arrowheads in panels C–F) and defective branching of the ureteric buds (black arrows in panels C–F).
Airik,
Tbx18 regulates the development of the ureteral mesenchyme.
2006, Pubmed
Airik,
Tbx18 regulates the development of the ureteral mesenchyme.
2006,
Pubmed
Balda,
Two classes of tight junctions are revealed by ZO-1 isoforms.
1993,
Pubmed
Balda,
Epithelial cell adhesion and the regulation of gene expression.
2003,
Pubmed
Basson,
Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction.
2005,
Pubmed
,
Xenbase
Berryman,
Ezrin is concentrated in the apical microvilli of a wide variety of epithelial cells whereas moesin is found primarily in endothelial cells.
1993,
Pubmed
Brault,
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
2001,
Pubmed
Brembeck,
Balancing cell adhesion and Wnt signaling, the key role of beta-catenin.
2006,
Pubmed
Brenner-Anantharam,
Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling.
2007,
Pubmed
Brophy,
Regulation of ureteric bud outgrowth by Pax2-dependent activation of the glial derived neurotrophic factor gene.
2001,
Pubmed
Costantini,
GDNF/Ret signaling and the development of the kidney.
2006,
Pubmed
Cox,
Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis.
1996,
Pubmed
DasGupta,
Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation.
1999,
Pubmed
Debiec,
Abnormal renal phenotype in L1 knockout mice: a novel cause of CAKUT.
2002,
Pubmed
Dressler,
Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system.
1990,
Pubmed
Fleming,
Assembly of tight junctions during early vertebrate development.
2000,
Pubmed
,
Xenbase
Gavert,
L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers.
2005,
Pubmed
Giles,
Caught up in a Wnt storm: Wnt signaling in cancer.
2003,
Pubmed
Grieshammer,
SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site.
2004,
Pubmed
Haegel,
Lack of beta-catenin affects mouse development at gastrulation.
1995,
Pubmed
Harada,
Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene.
1999,
Pubmed
He,
Identification of c-MYC as a target of the APC pathway.
1998,
Pubmed
Horne-Badovinac,
Positional cloning of heart and soul reveals multiple roles for PKC lambda in zebrafish organogenesis.
2001,
Pubmed
Huelsken,
beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
2001,
Pubmed
Iglesias,
Canonical WNT signaling during kidney development.
2007,
Pubmed
Jho,
Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway.
2002,
Pubmed
Kielman,
Apc modulates embryonic stem-cell differentiation by controlling the dosage of beta-catenin signaling.
2002,
Pubmed
Kume,
Murine forkhead/winged helix genes Foxc1 (Mf1) and Foxc2 (Mfh1) are required for the early organogenesis of the kidney and urinary tract.
2000,
Pubmed
Kurihara,
Diversity among tight junctions in rat kidney: glomerular slit diaphragms and endothelial junctions express only one isoform of the tight junction protein ZO-1.
1992,
Pubmed
Leung,
Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling.
2002,
Pubmed
Lustig,
Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors.
2002,
Pubmed
Maretto,
Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors.
2003,
Pubmed
Matter,
Mammalian tight junctions in the regulation of epithelial differentiation and proliferation.
2005,
Pubmed
Murtaugh,
Beta-catenin is essential for pancreatic acinar but not islet development.
2005,
Pubmed
Navarro,
Junctional recruitment of mammalian Scribble relies on E-cadherin engagement.
2005,
Pubmed
Park,
Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
2007,
Pubmed
Pepicelli,
GDNF induces branching and increased cell proliferation in the ureter of the mouse.
1997,
Pubmed
Perantoni,
Renal development: perspectives on a Wnt-dependent process.
2003,
Pubmed
Scheller,
Hematopoietic stem cell and multilineage defects generated by constitutive beta-catenin activation.
2006,
Pubmed
Schmidt-Ott,
beta-catenin/TCF/Lef controls a differentiation-associated transcriptional program in renal epithelial progenitors.
2007,
Pubmed
Shah,
Branching morphogenesis and kidney disease.
2004,
Pubmed
Shakya,
The role of GDNF in patterning the excretory system.
2005,
Pubmed
Sheth,
Tight junction assembly during mouse blastocyst formation is regulated by late expression of ZO-1 alpha+ isoform.
1997,
Pubmed
Shtutman,
The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway.
1999,
Pubmed
Soriano,
Generalized lacZ expression with the ROSA26 Cre reporter strain.
1999,
Pubmed
Towers,
Glial cell line-derived neurotrophic factor stimulates ureteric bud outgrowth and enhances survival of ureteric bud cells in vitro.
1998,
Pubmed
Willott,
Localization and differential expression of two isoforms of the tight junction protein ZO-1.
1992,
Pubmed
Woolf,
Evolving concepts in human renal dysplasia.
2004,
Pubmed
Woolf,
Renal hypoplasia and dysplasia: starting to put the puzzle together.
2006,
Pubmed
Yamaguchi,
Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse.
2006,
Pubmed
Yamamoto,
Expression of AQP family in rat kidneys during development and maturation.
1997,
Pubmed
Yu,
Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney.
2002,
Pubmed
,
Xenbase
Zechner,
beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system.
2003,
Pubmed
Zheng,
The induction of ret by Wnt-1 in PC12 cells is atypically dependent on continual Wnt-1 expression.
1996,
Pubmed
