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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
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
Summary
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.
- 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.
