Crosstalk between Jagged1 and GDNF/Ret/GFR[alpha]1 signalling regulates ureteric budding and branching

Satu Kuure, Kirsi Sainio, Reetta Vuolteenaho, Mika Ilves, Kirmo Wartiovaara, Tiina Immonen, Jouni Kvist, Seppo Vainio, Hannu Sariola

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Glial-Cell-Line-Derived Neurotrophic Factor (GDNF) is the major mesenchyme-derived regulator of ureteric budding and branching during nephrogenesis. The ligand activates on the ureteric bud epithelium a receptor complex composed of Ret and GFR alpha 1. The upstream regulators of the GDNF receptors are poorly known. A Notch ligand, Jagged1 (Jag1), co-localises with GDNF and its receptors during early kidney morphogenesis. In this study we utilized both in vitro and in vivo models to study the possible regulatory relationship of Ret and Notch pathways. Urogenital blocks were exposed to exogenous GDNF, which promotes supernumerary ureteric budding from the Wolffian duct. GDNF-induced ectopic buds expressed Jag1, which suggests that GDNF can, directly or indirectly, up-regulate Jag1 through Ret/GFR alpha 1 signalling. We then studied the role of Jag1 in nephrogenesis by transgenic mice constitutively expressing human Jag1 in Wolffian duct and its derivatives under HoxB7 promoter. Jag1 transgenic mice showed a spectrum of renal defects ranging from aplasia to hypoplasia. Ret and GFR alpha 1 are normally downregulated in the Wolffian duct, but they were persistently expressed in the entire transgenic duct. Simultaneously, GDNF expression remained unexpectedly low in the metanephric mesenchyme. In vitro, exogenous GDNF restored the budding and branching defects in transgenic urogenital blocks. Renal differentiation apparently failed because of perturbed stimulation of primary ureteric budding and subsequent branching. Thus, the data provide evidence for a novel crosstalk between Notch and Ret/GFR alpha 1 signalling during early nephrogenesis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
    Original languageEnglish
    JournalMechanisms of Development
    Volume122
    Pages (from-to)765-780
    Number of pages16
    ISSN0925-4773
    DOIs
    Publication statusPublished - 2005
    MoE publication typeA1 Journal article-refereed

    Cite this

    @article{1ec60eaa85014e8fba5d3cad73dd8758,
    title = "Crosstalk between Jagged1 and GDNF/Ret/GFR[alpha]1 signalling regulates ureteric budding and branching",
    abstract = "Glial-Cell-Line-Derived Neurotrophic Factor (GDNF) is the major mesenchyme-derived regulator of ureteric budding and branching during nephrogenesis. The ligand activates on the ureteric bud epithelium a receptor complex composed of Ret and GFR alpha 1. The upstream regulators of the GDNF receptors are poorly known. A Notch ligand, Jagged1 (Jag1), co-localises with GDNF and its receptors during early kidney morphogenesis. In this study we utilized both in vitro and in vivo models to study the possible regulatory relationship of Ret and Notch pathways. Urogenital blocks were exposed to exogenous GDNF, which promotes supernumerary ureteric budding from the Wolffian duct. GDNF-induced ectopic buds expressed Jag1, which suggests that GDNF can, directly or indirectly, up-regulate Jag1 through Ret/GFR alpha 1 signalling. We then studied the role of Jag1 in nephrogenesis by transgenic mice constitutively expressing human Jag1 in Wolffian duct and its derivatives under HoxB7 promoter. Jag1 transgenic mice showed a spectrum of renal defects ranging from aplasia to hypoplasia. Ret and GFR alpha 1 are normally downregulated in the Wolffian duct, but they were persistently expressed in the entire transgenic duct. Simultaneously, GDNF expression remained unexpectedly low in the metanephric mesenchyme. In vitro, exogenous GDNF restored the budding and branching defects in transgenic urogenital blocks. Renal differentiation apparently failed because of perturbed stimulation of primary ureteric budding and subsequent branching. Thus, the data provide evidence for a novel crosstalk between Notch and Ret/GFR alpha 1 signalling during early nephrogenesis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.",
    author = "Satu Kuure and Kirsi Sainio and Reetta Vuolteenaho and Mika Ilves and Kirmo Wartiovaara and Tiina Immonen and Jouni Kvist and Seppo Vainio and Hannu Sariola",
    year = "2005",
    doi = "10.1016/j.mod.2005.03.006",
    language = "English",
    volume = "122",
    pages = "765--780",
    journal = "Mechanisms of Development",
    issn = "0925-4773",
    publisher = "Elsevier Scientific Publ. Co",

    }

    Crosstalk between Jagged1 and GDNF/Ret/GFR[alpha]1 signalling regulates ureteric budding and branching. / Kuure, Satu; Sainio, Kirsi; Vuolteenaho, Reetta; Ilves, Mika; Wartiovaara, Kirmo; Immonen, Tiina; Kvist, Jouni; Vainio, Seppo; Sariola, Hannu.

    In: Mechanisms of Development, Vol. 122, 2005, p. 765-780.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Crosstalk between Jagged1 and GDNF/Ret/GFR[alpha]1 signalling regulates ureteric budding and branching

    AU - Kuure, Satu

    AU - Sainio, Kirsi

    AU - Vuolteenaho, Reetta

    AU - Ilves, Mika

    AU - Wartiovaara, Kirmo

    AU - Immonen, Tiina

    AU - Kvist, Jouni

    AU - Vainio, Seppo

    AU - Sariola, Hannu

    PY - 2005

    Y1 - 2005

    N2 - Glial-Cell-Line-Derived Neurotrophic Factor (GDNF) is the major mesenchyme-derived regulator of ureteric budding and branching during nephrogenesis. The ligand activates on the ureteric bud epithelium a receptor complex composed of Ret and GFR alpha 1. The upstream regulators of the GDNF receptors are poorly known. A Notch ligand, Jagged1 (Jag1), co-localises with GDNF and its receptors during early kidney morphogenesis. In this study we utilized both in vitro and in vivo models to study the possible regulatory relationship of Ret and Notch pathways. Urogenital blocks were exposed to exogenous GDNF, which promotes supernumerary ureteric budding from the Wolffian duct. GDNF-induced ectopic buds expressed Jag1, which suggests that GDNF can, directly or indirectly, up-regulate Jag1 through Ret/GFR alpha 1 signalling. We then studied the role of Jag1 in nephrogenesis by transgenic mice constitutively expressing human Jag1 in Wolffian duct and its derivatives under HoxB7 promoter. Jag1 transgenic mice showed a spectrum of renal defects ranging from aplasia to hypoplasia. Ret and GFR alpha 1 are normally downregulated in the Wolffian duct, but they were persistently expressed in the entire transgenic duct. Simultaneously, GDNF expression remained unexpectedly low in the metanephric mesenchyme. In vitro, exogenous GDNF restored the budding and branching defects in transgenic urogenital blocks. Renal differentiation apparently failed because of perturbed stimulation of primary ureteric budding and subsequent branching. Thus, the data provide evidence for a novel crosstalk between Notch and Ret/GFR alpha 1 signalling during early nephrogenesis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

    AB - Glial-Cell-Line-Derived Neurotrophic Factor (GDNF) is the major mesenchyme-derived regulator of ureteric budding and branching during nephrogenesis. The ligand activates on the ureteric bud epithelium a receptor complex composed of Ret and GFR alpha 1. The upstream regulators of the GDNF receptors are poorly known. A Notch ligand, Jagged1 (Jag1), co-localises with GDNF and its receptors during early kidney morphogenesis. In this study we utilized both in vitro and in vivo models to study the possible regulatory relationship of Ret and Notch pathways. Urogenital blocks were exposed to exogenous GDNF, which promotes supernumerary ureteric budding from the Wolffian duct. GDNF-induced ectopic buds expressed Jag1, which suggests that GDNF can, directly or indirectly, up-regulate Jag1 through Ret/GFR alpha 1 signalling. We then studied the role of Jag1 in nephrogenesis by transgenic mice constitutively expressing human Jag1 in Wolffian duct and its derivatives under HoxB7 promoter. Jag1 transgenic mice showed a spectrum of renal defects ranging from aplasia to hypoplasia. Ret and GFR alpha 1 are normally downregulated in the Wolffian duct, but they were persistently expressed in the entire transgenic duct. Simultaneously, GDNF expression remained unexpectedly low in the metanephric mesenchyme. In vitro, exogenous GDNF restored the budding and branching defects in transgenic urogenital blocks. Renal differentiation apparently failed because of perturbed stimulation of primary ureteric budding and subsequent branching. Thus, the data provide evidence for a novel crosstalk between Notch and Ret/GFR alpha 1 signalling during early nephrogenesis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

    U2 - 10.1016/j.mod.2005.03.006

    DO - 10.1016/j.mod.2005.03.006

    M3 - Article

    VL - 122

    SP - 765

    EP - 780

    JO - Mechanisms of Development

    JF - Mechanisms of Development

    SN - 0925-4773

    ER -