Epimorphin: a mesenchymal protein essential for epithelial morphogenesis

Y Hirai, K Takebe, M Takashina, S Kobayashi… - Cell, 1992 - cell.com
Y Hirai, K Takebe, M Takashina, S Kobayashi, M Takeichi
Cell, 1992cell.com
A novel 150 kd protein expressed on the surface of meaenchymai ceils of mouse embryonic
tissues was identified. A monoclonai antibody to this molecule inhibited various processes of
epitheiiai morphogeneais, such as hair follicle growth and lung epitheiiai tubular formation,
in organ cultures of these tissues. Sequence analysis of cDNA encoding this protein
revealed that it had 289 amino acids with a hydrophobic stretch at the C-terminus. NIH 3T3
ceils tranafected with the cDNA of this protein expressed the exogenous 150 kd protein on …
Summary
A novel 150 kd protein expressed on the surface of meaenchymai ceils of mouse embryonic tissues was identified. A monoclonai antibody to this molecule inhibited various processes of epitheiiai morphogeneais, such as hair follicle growth and lung epitheiiai tubular formation, in organ cultures of these tissues. Sequence analysis of cDNA encoding this protein revealed that it had 289 amino acids with a hydrophobic stretch at the C-terminus. NIH 3T3 ceils tranafected with the cDNA of this protein expressed the exogenous 150 kd protein on their surface. When lung epithelial ceils were cocultured with these transfected ceils, they showed normal tubular morphogeneais, but not with untransfected NIH 3T3 ceils. These results indicate that this protein, termed epimorphin, plays a central role in epitheiiai-mesenchymal interactions. introduction
Histogenesisof embryonic tissues is governed by complex cell-cell interactions. The epithelial-mesenchymal interaction is one of such interactions. Epithelia are always surrounded by mesenchymal cells, and some signals are transmitted from mesenchyme to epithelia or vice versa for these tissues to differentiate properly (Deuchar, 1975; Wessels, 1977; Sawer and Fallon, 1983). The roles of mesenchyme in such interactions have been studied extensively using various tissues such as skin (Dhouailiy et al., 1978; Hardy et al., 1983; Jahoda and Oliver, 1984), mammary gland (Sakakura et al., 1976; Bissell and Hall, 1987) salivary gland (Nogawa and Mizuno, 1981), kidney (Saxen and Sariola, 1987) lung (Wessels, 1977) and the digestive system (Takiguchi et al., 1988; Mizuno and Yasugi, 1990). Mesenchyme of these tissues supports growth and differentiation of the adjacent epithelia, and, in general, embryonic epithelial cells cannot undergo normal development without mesenchymal signals. Postulated mesenchymal factors includesome componentsof extracellular matrices (ECMs)(Bissell etal., 1982) cellsurface-associated molecules (Sariola et al., 1988) and soluble factors (Mercola
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