ArticleDevelopmental biology2012
A protein kinase A and Wnt-dependent network regulating an intermediate stage in epithelial tubulogenesis during kidney development.
Article in Developmental biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Advances in the Treatment of Autosomal Dominant Polycystic Kidney Disease and Novel Therapeutic Targets.Current issues in molecular biology · 2026Review
- MRPS16 Regulates NFATC2 Through the Wnt/β-Catenin Pathway to Promote Glioma Proliferation.Journal of cellular and molecular medicine · 2026Article
- Disturbances in Switching between Canonical and Non-Canonical Wnt Signaling Characterize Developing and Postnatal Kidneys ofBiomedicines · 2023Article
- Overexpression of long noncoding RNAFrontiers in cell and developmental biology · 2023Article
- Therapeutic advances in ADPKD: the future awaits.Journal of nephrology · 2022Review
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.The Journal of clinical investigation · 2021Article
- Wnt-induced activation of glucose metabolism mediates the in vivo neuroprotective roles of Wnt signaling in Alzheimer disease.Journal of neurochemistry · 2019Article
- HGF promotes HTR-8/SVneo cell migration through activation of MAPK/PKA signaling leading to up-regulation of WNT ligands and integrins that target β-catenin.Molecular and cellular biochemistry · 2019Article
- Cenani-Lenz syndactyly syndrome - a case report of a family with isolated syndactyly.BMC medical genetics · 2018Article
- Wnt Signaling in Kidney Development and Disease.Progress in molecular biology and translational science · 2018Review
- Ectopic Phosphorylated Creb Marks Dedifferentiated Proximal Tubules in Cystic Kidney Disease.The American journal of pathology · 2018Article
- The interaction of Wnt-11 and signalling cascades in prostate cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- The multi-omic landscape of transcription factor inactivation in cancer.Genome medicine · 2016Article
- Article
- Novel therapeutic approaches to autosomal dominant polycystic kidney disease.Translational research : the journal of laboratory and clinical medicine · 2015Review
- Detection of abnormal extracellular matrix in the interstitium of regenerating renal tubules.International journal of molecular sciences · 2014Article
- Phosphodiesterase 1A modulates cystogenesis in zebrafish.Journal of the American Society of Nephrology : JASN · 2014Article
- Coordination of kidney organogenesis by Wnt signaling.Pediatric nephrology (Berlin, Germany) · 2014Review
- Wnt/β-catenin signaling modulates human airway sensitization induced by β2-adrenoceptor stimulation.PloS one · 2014Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Genetic interactions regulating intermediate stages of tubulogenesis in the developing kidney have been difficult to define. A systems biology strategy using microarray was combined with in vitro/ex vivo and genetic approaches to identify pathways regulating specific stages of tubulogenesis. Analysis of the progression of the metanephric mesenchyme (MM) through four stages of tubule induction and differentiation (i.e., epithelialization, tubular organization and elongation and early differentiation) revealed signaling pathways potentially involved at each stage and suggested key roles for a number of signaling molecules. A screen of the signaling pathways on in vitro/ex vivo nephron formation implicated a unique regulatory role for protein kinase A (PKA), through PKA-2, in a specific post-epithelialization morphogenetic step (conversion of the renal vesicle to the S-shaped body). Microarray analysis not only confirmed this stage-specificity, but also highlighted the upregulation of Wnt genes. Addition of PKA agonists to LIF-induced nephrons (previously shown to be a Wnt/beta-catenin dependent pathway) disrupted normal tubulogenesis in a manner similar to PKA-agonist treated MM/spinal-cord assays, suggesting that PKA regulates a Wnt-dependent tubulogenesis step. PKA induction of canonical Wnt signaling during tubulogenesis was confirmed genetically using MM from Batgal-reporter mice. Addition of a Wnt synthesis inhibitor to activated PKA cultures rescued tubulogenesis. By re-analysis of existing microarray data from the FGF8, Lim1 and Wnt4 knockouts, which arrest in early tubulogenesis, a network of genes involving PKA, Wnt, Lhx1, FGF8, and hyaluronic acid signaling regulating the transition of nascent epithelial cells to tubular epithelium was derived, helping to reconcile in vivo and in vitro/ex vivo data.
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