COEXPRESSION OF THE HGF SF AND C-MET GENES DURING EARLY MOUSE EMBRYOGENESIS PRECEDES RECIPROCAL EXPRESSION IN ADJACENT TISSUES DURING ORGANOGENESIS/

Early experiments with cells in culture and recent targeting experimen ts have confirmed that the mesenchyme-derived growth factor hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine agent that regul ates the development of several epithelial and myogenic precursor cell s during organogenesis. Here, we report the expression pattern of HGF/ SF and its receptor, the product of the proto-oncogene c-met, during g astrulation and early organogenesis in mouse embryo. During gastrulati on, the expression of HGF/SF and c-met overlaps. Initially the two gen es are expressed in the endoderm and in the mesoderm along the rostro- intermediate part of the primitive streak and, later, in the node and in the notochord. Neither HGF/SF nor c-met is expressed in the ectoder mal layer throughout gastrulation. During early organogenesis, overlap ping expression of HGF/SF and c-met is found in heart, condensing somi tes and neural crest cells. However, a second and distinct pattern of expression, characterized by the presence of the ligand in mesenchymal tissues and the receptor in the surrounding ectoderm, is seen in the branchial arches and in the limb buds. At 13 days postcoitum (d.p.c.), only this second pattern of expression is observed in differentiated somites and several major organs (i.e., lungs, liver, and gut). The ex pression of the HGF/SF and c-met genes throughout embryogenesis sugges ts a shift from an autocrine to a paracrine signaling system. The shif t takes place in early organogenesis and implies different roles of HG F/SF in development. During gastrulation, HGF/SF may affect the fate o f migrating mesodermal cells and may play a role in axis determination , whereas during organogenesis, the expression patterns of HGF/SF and its receptor reflect the recently established roles in the growth of c ertain epithelia and the migration of specific myogenic precursor cell s. (C) 1996 Wiley-Liss, Inc.