Disruption of polycystin-1 function interferes with branching morphogenesis of the ureteric bud in developing mouse kidneys.

The polycystic kidney disease (PKD1) gene-encoded protein, polycystin-1, is developmentally regulated, with highest expression levels seen in normal developing kidneys, where it is distributed in a punctate pattern at the basal surface of ureteric bud epithelia. Overexpression in ureteric epithelial cell membranes of an inhibitory pMyr-GFP-PKD1 fusion protein via a retroviral (VVC) delivery system and microinjection into the ureteric bud lumen of embryonic day 11 mouse metanephric kidneys resulted in disrupted branching morphogenesis. Using confocal quantitative analysis, significant reductions were measured in the numbers of ureteric bud branch points and tips, as well as in the total ureteric bud length, volume and area, while significant increases were seen as dilations of the terminal branches, where significant increases in outer diameter and volumes were measured. Microinjection of an activating 5TM-GFP-PKD1 fusion protein had an opposite effect and showed significant increases in ureteric bud length and area. These are the first studies to experimentally manipulate polycystin-1 expression by transduction in the embryonic mouse kidney and suggest that polycystin-1 plays a critical role in the regulation of epithelial morphogenesis during renal development.

• Publication year

  2005

• Venue

  Developmental Biology

• Publication date

  2005-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/J.YDBIO.2005.06.034PMID 16122726
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Polycystic kidney disease.

  2004cited by this paper
• Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells

  2003cited by this paper
• Na transport in autosomal recessive polycystic kidney disease (ARPKD) cyst lining epithelial cells.

  2003cited by this paper
• A polycystin-1 multiprotein complex is disrupted in polycystic kidney disease cells.

  2003influential reference
• Towards Understanding the Polycystins

  2003cited by this paper
• The polycystin-1 C-terminal fragment triggers branching morphogenesis and migration of tubular kidney epithelial cells.

  2002cited by this paper
• Organogenesis: Coordinating early kidney development: lessons from gene targeting

  2002cited by this paper
• Adhesion assembly, disassembly and turnover in migrating cells – over and over and over again

  2002cited by this paper
• The molecular control of renal branching morphogenesis: current knowledge and emerging insights.

  2002cited by this paper
• Morphogenesis of the Metanephric Kidney

  2002cited by this paper
• The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia.

  2002cited by this paper
• Interaction of the leucine-rich repeats of polycystin-1 with extracellular matrix proteins: possible role in cell proliferation.

  2002cited by this paper
• The polycystin-1 C-type lectin domain binds carbohydrate in a calcium-dependent manner, and interacts with extracellular matrix proteins in vitro.

  2001cited by this paper
• Nephrocystin interacts with Pyk2, p130Cas, and tensin and triggers phosphorylation of Pyk2

  2001cited by this paper
• Downregulation of Jun kinase signaling in the amnioserosa is essential for dorsal closure of the Drosophila embryo.

  2001cited by this paper
• Coordination of cell polarization and migration by the Rho family GTPases requires Src tyrosine kinase activity.

  2001cited by this paper
• Differential Dynamics of α5 Integrin, Paxillin, and α-Actinin during Formation and Disassembly of Adhesions in Migrating Cells

  2001cited by this paper
• Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene

  2001cited by this paper
• Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease.

  2000cited by this paper
• Polycystin 1 is required for the structural integrity of blood vessels.

  2000cited by this paper
• Compromised Cytoarchitecture and Polarized Trafficking in Autosomal Dominant Polycystic Kidney Disease Cells

  2000influential reference
• Apical plasma membrane mispolarization of NaK-ATPase in polycystic kidney disease epithelia is associated with aberrant expression of the beta2 isoform.

  2000cited by this paper
• Regulatory molecules in kidney development

  2000cited by this paper
• Modification of the composition of polycystin-1 multiprotein complexes by calcium and tyrosine phosphorylation.

  2000cited by this paper
• Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells.

  2000cited by this paper
• The PKD1 gene product, "polycystin-1," is a tyrosine-phosphorylated protein that colocalizes with alpha2beta1-integrin in focal clusters in adherent renal epithelia.

  1999cited by this paper
• Identification of phosphorylation sites in the PKD1-encoded protein C-terminal domain.

  1999cited by this paper
• A new syndrome: Heart defects, laryngeal anomalies, preaxial polydactyly, and colonic aganglionosis in sibs

  1999cited by this paper
• The structure of a PKD domain from polycystin‐1: implications for polycystic kidney disease

  1999cited by this paper
• The Polycystic Kidney Disease 1 Gene Product Modulates Wnt Signaling*

  1999influential reference
• Signal transduction by the c-Jun N-terminal kinase.

  1999cited by this paper
• Roles of protein tyrosine phosphatases in cell migration and adhesion.

  1999cited by this paper
• Overexpression of c-Src enhances cell-matrix adhesion and cell migration in PDGF-stimulated NIH3T3 fibroblasts.

  1999cited by this paper
• Polycystin-1, the PKD1 gene product, is in a complex containing E-cadherin and the catenins.

  1999cited by this paper
• Prenatal diagnosis of autosomal dominant polycystic kidney disease (PKD1) presenting in utero and prognosis for very early onset disease.

  1998cited by this paper
• The polycystic kidney disease-1 protein, polycystin-1, binds and activates heterotrimeric G-proteins in vitro.

  1998cited by this paper
• The Polycystic Kidney Disease-1 Protein, Polycystin-1, Binds and Activates Heterotrimeric G-Proteinsin Vitro

  1998cited by this paper
• The Polycystic Kidney Disease 1 Gene Product Mediates Protein Kinase C α-dependent and c-Jun N-terminal Kinase-dependent Activation of the Transcription Factor AP-1*

  1998cited by this paper
• Identification of p130Cas as a Mediator of Focal Adhesion Kinase–promoted Cell Migration

  1998cited by this paper
• Epithelial cell polarity and disease.

  1997cited by this paper
• Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation

  1997cited by this paper
• Polycystin expression is temporally and spatially regulated during renal development.

  1997cited by this paper
• Distribution and developmentally regulated expression of murine polycystin.

  1997influential reference
• Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney.

  1996cited by this paper
• Metanephros organogenesis is highly stimulated by vitamin A derivatives in organ culture.

  1996influential reference
• Abnormalities in extracellular matrix regulation in autosomal dominant polycystic kidney disease.

  1996cited by this paper
• In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector

  1996cited by this paper
• Renal proximal tubular epithelium from patients with nephropathic cystinosis: immortalized cell lines as in vitro model systems.

  1995cited by this paper
• Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice

  1995cited by this paper
• Tensin: A potential link between the cytoskeleton and signal transduction

  1994cited by this paper
• Tubular cell and matrix changes in renal cystic disease.

  1993cited by this paper
• Abnormal extracellular matrix and excessive growth of human adult polycystic kidney disease epithelia

  1992cited by this paper
• Reversed polarity of Na(+) -K(+) -ATPase: mislocation to apical plasma membranes in polycystic kidney disease epithelia.

  1991cited by this paper
• Autosomal dominant polycystic kidney disease in childhood: a longitudinal study.

  1987cited by this paper
• Growth factor requirements of organogenesis in serum-free metanephric organ culture

  1985influential reference
• Defined human renal tubular epithelia in culture: growth, characterization, and hormonal response.

  1985cited by this paper
• Transferrin as a fetal growth factor: acquisition of responsiveness related to embryonic induction.

  1983influential reference

• Hypoxia induces polycystin-1 expression in the renal epithelium

  2023cites this paper
• Urinary exosome proteomic profiling defines stage-specific rapid progression of autosomal dominant polycystic kidney disease and tolvaptan efficacy.

  2021cites this paper
• Urinary exosomes protein cargo as biomarkers of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

  2020cites this paper
• Metanephric organ culture.

  2019cites this paper
• The association between autosomal dominant polycystic kidney disease and cancer

  2018cites this paper
• Gαi-mediated TRPC4 activation by polycystin-1 contributes to endothelial function via STAT1 activation

  2018cites this paper
• The regulatory 1α subunit of protein kinase A modulates renal cystogenesis.

  2017cites this paper
• TRAF3 delays cyst formation induced by NF‐κB signaling

  2017cites this paper
• Src family kinases in chronic kidney disease.

  2017cites this paper
• Therapeutic targets for polycystic kidney disease

  2016cites this paper
• Characterisation of pathophysiological function of NEDD4-2 in kidney

  2016cites this paper
• Impaired glomerulogenesis and endothelial cell migration in Pkd1-deficient renal organ cultures

  2014cites this paper
• Shaping up for action

  2013cites this paper
• Overexpression of Robo2 causes defects in the recruitment of metanephric mesenchymal cells and ureteric bud branching morphogenesis.

  2012cites this paper
• c-Src inactivation reduces renal epithelial cell-matrix adhesion, proliferation, and cyst formation.

  2011cites this paper
• Receptor protein tyrosine phosphatases are novel components of a polycystin complex.

  2011cites this paper
• Apico-basal polarity in polycystic kidney disease epithelia.

  2011cites this paper
• Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD).

  2011cites this paper
• Abnormalities in focal adhesion complex formation, regulation, and function in human autosomal recessive polycystic kidney disease epithelial cells.

  2010cites this paper
• In Vitro Methods in Renal Research

  2009cites this paper
• THE ROLE OF TIGHT JUNCTION PROTEINS CLAUDIN-3 AND CLAUDIN-7 IN URETERIC BUD BRANCHING

  2009cites this paper
• Protein kinase-X interacts with Pin-1 and Polycystin-1 during mouse kidney development.

  2009cites this paper
• Novel role for polycystin‐1 in modulating cell proliferation through calcium oscillations in kidney cells

  2008cites this paper
• [Autosomal dominant polycystic kidney disease].

  2008cites this paper
• Defects in ciliary localization of Nek8 is associated with cystogenesis

  2008cites this paper
• Protein kinase X (PRKX) can rescue the effects of polycystic kidney disease-1 gene (PKD1) deficiency.

  2008cites this paper
• Mouse models of polycystic kidney disease.

  2008influential citation
• Cystic disease of the kidney.

  2007cites this paper
• Mouse embryonic stem cell-derived embryoid bodies generate progenitors that integrate long term into renal proximal tubules in vivo.

  2007cites this paper
• Renal branching morphogenesis: concepts, questions, and recent advances.

  2006cites this paper
• Inhibition of HER-2(neu/ErbB2) restores normal function and structure to polycystic kidney disease (PKD) epithelia.

  2006cites this paper
• Mechanisms of Disease: autosomal dominant and recessive polycystic kidney diseases

  2006cites this paper