ArticleDevelopmental biology2011
Wnt4 induces nephronic tubules in metanephric mesenchyme by a non-canonical mechanism.
Article in Developmental biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 125 citations in OpenAlex.
- Review
- Stn1 promotes zebrafish oocyte development via amplifying Wnt/β-catenin signaling.EMBO reports · 2026Article
- Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling.Cell stem cell · 2025Article
- Pharmacological modulation of stem cells signaling pathway for therapeutic applications.Stem cell research & therapy · 2025Review
- Disruption of Notch signaling by KGF induces a developmental pause in thymocytes.Frontiers in immunology · 2025Article
- Deciphering the cellular and molecular landscapes of Wnt/β-catenin signaling in mouse embryonic kidney development.Computational and structural biotechnology journal · 2024Article
- Dynamic Kidney Organoid Microphysiological Analysis Platform.bioRxiv : the preprint server for biology · 2024Article
- Cadherin adhesion complexes direct cell aggregation in the epithelial transition of Wnt-induced nephron progenitor cells.Development (Cambridge, England) · 2024Article
- Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).Kidney international · 2024Article
- Loss of Dact2 alleviates cisplatin-induced nephrotoxicity through regulation of the Igfl-MAPK pathway axis.Cell biology and toxicology · 2023Article
- Wnt signaling regulates ion channel expression to promote smooth muscle and cartilage formation in developing mouse trachea.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.Disease models & mechanisms · 2023Article
- Wnt signaling regulates ion channel expression to promote smooth muscle and cartilage formation in developing mouse trachea.bioRxiv : the preprint server for biology · 2023Article
- Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function.Nature communications · 2022Article
- Principles of human and mouse nephron development.Nature reviews. Nephrology · 2022Review
- Planar cell polarity pathway in kidney development, function and disease.Nature reviews. Nephrology · 2021Review
- Returning to kidney development to deliver synthetic kidneys.Developmental biology · 2021Review
- Review
- Wnt signaling in kidney: the initiator or terminator?Journal of molecular medicine (Berlin, Germany) · 2020Review
- Stem cell-derived kidney organoids: engineering the vasculature.Cellular and molecular life sciences : CMLS · 2020Review
13 more citing papers are in PubMed but not listed here.
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9 authors at 3 institutions in 1 country.
Funding
Abstract
Wnt4 and β-catenin are both required for nephrogenesis, but studies using TCF-reporter mice suggest that canonical Wnt signaling is not activated in metanephric mesenchyme (MM) during its conversion to the epithelia of the nephron. To better define the role of Wnt signaling, we treated rat metanephric mesenchymal progenitors directly with recombinant Wnt proteins. These studies revealed that Wnt4 protein, which is required for nephron formation, induces tubule formation and differentiation markers Lim1 and E-cadherin in MM cells, but does not activate a TCF reporter or up regulate expression of canonical Wnt target gene Axin-2 and has little effect on the stabilization of β-catenin or phosphorylation of disheveled-2. Furthermore, Wnt4 causes membrane localization of ZO-1 and occludin in tight junctions. To directly examine the role of β-catenin/TCF-dependent transcription, we developed synthetic cell-permeable analogs of β-catenin's helix C, which is required for transcriptional activation, in efforts to specifically inhibit canonical Wnt signaling. One inhibitor blocked TCF-dependent transcription and induced degradation of β-catenin but did not affect tubule formation and stimulated the expression of Lim1 and E-cadherin. Since a canonical mechanism appears not to be operative in tubule formation, we assessed the involvement of the non-canonical Ca(2+)-dependent pathway. Treatment of MM cells with Wnt4 induced an influx of Ca(2+) and caused phosphorylation of CaMKII. Moreover, Ionomycin, a Ca(2+)-dependent pathway activator, stimulated tubule formation. These results demonstrate that the canonical Wnt pathway is not responsible for mesenchymal-epithelial transition (MET) in nephron formation and suggest that the non-canonical calcium/Wnt pathway mediates Wnt4-induced tubulogenesis in the kidney.
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