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Expression of HGF/SF, HGF1/MSP, and c-met suggests new functions during early chick development
C Théry1, M J Sharpe, S J Batley
1Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Abstract:
We report the cloning of fulllength cDNAs for a plasminogen-related growth factor, hepatocyte growth factor/scatter factor (HGF/SF), its tyrosine kinase receptor, c-met, and a close member of the same family, hepatocyte growth factor-like/macrophage stimulating protein (HGF1/MSP), from the chick. We have used these cDNAs to provide the first report of the expression of this family of growth factors and the c-met receptor at early stages of vertebrate development. RNAase protection and wholemount in situ hybridization were used on chick embryos between formation of the primitive streak and early organogenesis. We find patterns of expression for HGF/SF and its receptor c-met consistent with their known roles in epithelial-mesenchymal transformation and angiogenesis. In addition, these genes and HGF1/MSP are expressed in discrete locations within developing somites, suggesting a role in paraxial mesodermal development. Very strong and early expression of HGF/SF in the elevating limb buds suggests its involvement in limb outgrowth. HGF1/MSP is expressed in the notochord and then in the prospective floor plate region and could play a role in development of the neural tube. Interestingly, c-met is often more closely associated with HGF1/MSP than with its known ligand, HGF/SF, raising the possibility that c-met expression may be induced by HGF1/MSP.
Insights
This study details the cloning and early expression patterns of chick hepatocyte growth factor/scatter factor (HGF/SF), its receptor c-met, and HGF1/MSP. Findings suggest roles in embryonic development, including limb outgrowth and neural tube formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Signaling
Background:
- Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-met are crucial for epithelial-mesenchymal transitions and angiogenesis.
- Hepatocyte growth factor-like/macrophage stimulating protein (HGF1/MSP) is a related growth factor with less understood developmental roles.
Purpose of the Study:
- To clone full-length cDNAs for chick HGF/SF, c-met, and HGF1/MSP.
- To investigate the early expression patterns of these genes and the c-met receptor during chick embryonic development.
- To explore potential novel roles for HGF/SF, c-met, and HGF1/MSP in vertebrate embryogenesis.
Main Methods:
- Cloning of full-length cDNAs for HGF/SF, c-met, and HGF1/MSP from the chick.
- RNAase protection assays to quantify gene expression.
- Whole-mount in situ hybridization to visualize spatial expression patterns in chick embryos.
Main Results:
- HGF/SF and c-met expression patterns align with known roles in epithelial-mesenchymal transformation and angiogenesis.
- HGF/SF shows strong early expression in developing limb buds, suggesting involvement in limb outgrowth.
- HGF1/MSP and c-met exhibit distinct expression patterns in somites, notochord, and neural tube, indicating roles in paraxial mesoderm and neural development.
- c-met expression was sometimes more closely associated with HGF1/MSP than HGF/SF, suggesting potential alternative signaling pathways.
Conclusions:
- The HGF/SF-c-met and HGF1/MSP signaling pathways are dynamically expressed during early chick development.
- These factors likely play significant roles in diverse developmental processes, including somite formation, limb development, and neural tube patterning.
- The observed expression patterns suggest HGF1/MSP may influence c-met expression, potentially expanding the known signaling network.