PATTERN OF KERATINOCYTE GROWTH-FACTOR AND KERATINOCYTE GROWTH-FACTOR RECEPTOR EXPRESSION DURING MOUSE FETAL DEVELOPMENT SUGGESTS A ROLE IN MEDIATING MORPHOGENETIC MESENCHYMAL EPITHELIAL INTERACTIONS

Mesenchymal cells are required for the induction of epithelial develop ment during mammalian organogenesis. Keratinocyte growth factor (KGF) is a mesenchymally derived mitogen with specific activity for epitheli al cells, suggesting that it may play a role in mediating these intera ctions. To further evaluate this hypothesis, in situ hybridization was used to examine the spatial distribution of KGF and KGF receptor (KGF R) transcripts during organogenesis and limb formation in mouse embryo s (days 14.5 through 16.5). To facilitate this aim, mouse KGF cDNA clo nes were isolated. There was extensive identity between the deduced mo use KGF protein sequence and that of its human and rat cognates, indic ating that this gene has been highly conserved during mammalian evolut ion. In addition, mouse KGF protein was purified from fibroblasts and demonstrated to be structurally and functionally similar to human KGF protein. For organs within the integumental, respiratory, gastrointest inal, and urogenital systems, whose development is dependent upon mese nchymal-epithelial interactions, KGF mRNA was detected in mesenchymal cells, while epithelial cells expressed transcripts for the KGFR. KGF and KGFR mRNA was also expressed in certain other tissues such as peri chondrium, cartilage of developing bones, developing skeletal muscle, and visceral smooth muscle whose development is not regulated by mesen chymal-epithelial interactions. KGF expression was also detected in ti ssues isolated from human embryos, suggesting similar functions for KG F in human development. Taken together, our results suggest that KGF p lays an important role in mediating mesenchymal-epithelial interaction s during organogenesis, but may also have other developmental function s in tissues not governed by such interactions. (C) 1995 Wiley-Liss, I nc.