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Related Experiment Videos

Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney.

C E Fisher1, L Michael, M W Barnett

  • 1Centre for Developmental Biology, Department of Biomedical Sciences, University of Edinburgh, George Square, Edinburgh, UK.

Development (Cambridge, England)
|October 31, 2001
PubMed
Summary
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The mitogen-activated protein (MAP) kinase pathway, specifically Erk, is crucial for epithelial branching during kidney development. Inhibiting Erk signaling reversibly halts branching morphogenesis in the ureteric bud.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Organogenesis

Background:

  • Branching morphogenesis is vital for organ development, including kidney collecting ducts.
  • Mesenchyme-derived molecules regulate epithelial development, but their integration is not fully understood.
  • Cytoplasmic signal transduction networks, like the MAP kinase pathway, may integrate these signals.

Purpose of the Study:

  • To investigate the role of the MAP kinase pathway in mammalian ureteric bud branching.
  • To determine if Erk MAP kinase is essential for kidney development's branching morphogenesis.

Main Methods:

  • Studied the ureteric bud of the metanephric kidney, a model for branching morphogenesis.
  • Inhibited Erk MAP kinase activation using the MAP kinase kinase inhibitor PD98059.

Related Experiment Videos

  • Assessed effects on branching, tubule elongation, cell proliferation, actin filaments, and apoptosis.

    • Main Results:

    • Erk MAP kinase is active in the ureteric bud.
    • Inhibiting Erk activation reversibly blocked ureteric bud branching in a dose-dependent manner.
    • Erk inhibition reduced cell proliferation and laminin-rich processes, but did not affect apoptosis or Ret/Ros expression.

    Conclusions:

    • The Erk MAP kinase pathway is essential for normal branching morphogenesis of the ureteric bud.
    • Erk pathway activity depends on GDNF-Ret signaling and sulphated glycosaminoglycans.
    • MAP kinase acts downstream of extracellular regulators in ureteric bud development.