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

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

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

C E Fisher,L Michael,M W Barnett,J A Davies,

Branching morphogenesis of epithelium is a common and important feature of organogenesis; it is, for example, responsible for development of renal collecting ducts, lung airways, milk ducts of mammary glands and seminal ducts of the prostate. In each case, epithelial development is controlled by a variety of mesenchyme-derived molecules, both soluble (e.g. growth factors) and insoluble (e.g. extracellular matrix). Little is known about how these varied influences are integrated to produce a coherent morphogenetic response, but integration is likely to be achieved at least partly by cytoplasmic signal transduction networks. Work in other systems (Drosophila tracheae, MDCK models) suggests that the mitogen-activated protein (MAP) kinase pathway might be important to epithelial branching. We have investigated the role of the MAP kinase pathway in one of the best characterised mammalian examples of branching morphogenesis, the ureteric bud of the metanephric kidney. We find that Erk MAP kinase is normally active in ureteric bud, and that inhibiting Erk activation with the MAP kinase kinase inhibitor, PD98059, reversibly inhibits branching in a dose-dependent manner, while allowing tubule elongation to continue. When Erk activation is inhibited, ureteric bud tips show less cell proliferation than controls and they also produce fewer laminin-rich processes penetrating the mesenchyme and fail to show the strong concentration of apical actin filaments typical of controls; apoptosis and expression of Ret and Ros, are, however, normal. The activity of the Erk MAP kinase pathway is dependent on at least two known regulators of ureteric bud branching; the GDNF-Ret signalling system and sulphated glycosaminoglycans. MAP kinase is therefore essential for normal branching morphogenesis of the ureteric bud, and lies downstream of significant extracellular regulators of ureteric bud development.

Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney. Publishing Authors By Initials

CE Fisher,L Michael,MW Barnett,JA Davies,

For similar urogenital system: urinary tract: ureter research abstracts see: urogenital system: urinary tract: ureter research

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Development (Cambridge, England)

VOLUME: 128

Page Numbers: 4329-38

Journal Abbreviation: Development

ISSN: 0950-1991

DAY: 19

MONTH: Nov

YEAR: 2001

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 8701744

Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney. Keywords Mesh Terms:

KEYWORDS: Ureter

MESH TERMS: metabolism

Chemical & Substance for Abstract: Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney. Information

Substance Name: Mitogen-Activated Protein Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney.

AFFILIATION: Centre for Developmental Biology, Department of Biomedical Sciences, University of Edinburgh, George Square, Edinburgh, UK.

Country: England

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MEDLINETA: Development

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