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Tyrosine kinase receptors in the control of epithelial growth and morphogenesis during development
C Birchmeier1, E Sonnenberg, K M Weidner
1Max-Delbrück-Laboratorium, Max-Planck-Gesellschaft, Köln, Germany.
Abstract:
The c-ros, c-met and c-neu genes encode receptor-type tyrosine kinases and were originally identified because of their oncogenic potential. However, recent progress in the analysis of these receptors and their respective ligands indicate that they do not mediate exclusively mitogenic signals. Rather, they can induce cell movement, differentiation or morphogenesis of epithelial cells in culture. Interestingly, the discussed receptors are expressed in embryonal epithelia, whereas direct and indirect evidence shows that the corresponding ligands are produced in mesenchymal cells. In development, signals given by mesenchymal cells are major driving forces for differentiation and morphogenesis of epithelia; embryonal epithelia are generally unable to differentiate without the appropriate mesenchymal factors. The observed activities of these receptor/ligand systems in cultured cells and their expression patterns indicate that they regulate epithelial differentiation and morphogenesis also during embryogenesis and suggest thus a molecular basis for mesenchymal epithelial interactions.
Insights
Receptor tyrosine kinases like c-ros, c-met, and c-neu regulate epithelial cell movement and differentiation. Their signaling, influenced by mesenchymal factors, is crucial for embryonic development and epithelial morphogenesis.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Signaling
Background:
- The c-ros, c-met, and c-neu genes encode receptor-type tyrosine kinases initially recognized for oncogenic properties.
- Recent findings reveal these receptors mediate diverse signals beyond mitogenesis, including cell movement, differentiation, and morphogenesis in epithelial cells.
Purpose of the Study:
- To investigate the role of c-ros, c-met, and c-neu receptor tyrosine kinases and their ligands in epithelial development.
- To elucidate the molecular mechanisms underlying mesenchymal-epithelial interactions during embryogenesis.
Main Methods:
- Analysis of receptor and ligand expression patterns in embryonal epithelia and mesenchymal cells.
- Functional studies of receptor-ligand systems in cultured epithelial cells to assess signaling outcomes.
Main Results:
- Receptor tyrosine kinases (RTKs) c-ros, c-met, and c-neu are expressed in embryonal epithelia.
- Their corresponding ligands are produced by mesenchymal cells, suggesting a paracrine signaling mechanism.
- These RTK/ligand systems induce epithelial cell differentiation and morphogenesis in vitro.
Conclusions:
- Mesenchymal-derived signals acting through RTKs regulate epithelial differentiation and morphogenesis during embryogenesis.
- These findings establish a molecular basis for critical mesenchymal-epithelial interactions in development.