SCATTER FACTOR HEPATOCYTE GROWTH-FACTOR AND ITS RECEPTOR, THE C-MET TYROSINE KINASE, CAN MEDIATE A SIGNAL EXCHANGE BETWEEN MESENCHYME AND EPITHELIA DURING MOUSE DEVELOPMENT

Scatter factor/hepatocyte growth factor (SF/HGF) has potent motogenic, mitogenic, and morphogenetic activities on epithelial cells in vitro. The cell surface receptor for this factor was recently identified: it is the product of the c-met protooncogene, a receptor-type tyrosine k inase. We report here the novel and distinct expression patterns of SF /HGF and its receptor during mouse development, which was determined b y a combination of in situ hybridization and RNase protection experime nts. Predominantly, we detect transcripts of c-met in epithelial cells of various developing organs, whereas the ligand is expressed in dist inct mesenchymal cells in close vicinity. In addition, transient SF/HG F and c-met expression is found at certain sites of muscle formation; transient expression of the c-met gene is also detected in developing motoneurons. SF/HGF and the c-met receptor might thus play multiple de velopmental roles, most notably, mediate a signal given by mesenchyme and received by epithelial. Mesenchymal signals are known to govern di fferentiation and morphogenesis of many epithelia, but the molecular n ature of the signals has remained poorly understood. Therefore, the kn own biological activities of SF/HGF in vitro and the embryonal express ion pattern reported here indicate that this mesenchymal factor can tr ansmit morphogenetic signals in epithelial development and suggest a m olecular mechanism for mesenchymal epithelial interactions.