BRANCHING MORPHOGENESIS OF EMBRYONIC MOUSE LUNG EPITHELIUM IN MESENCHYME-FREE CULTURE

Embryonic mouse lung epithelium was separated from its mesenchyme and cultured under mesenchyme-free conditions. When covered with Matrigel, the cultured epithelium underwent branching morphogenesis in medium c ontaining acidic fibroblast growth factor (aFGF), in which the epithel ial cells constructed a simple columnar cell layer forming a lumen, as seen in normal development. The epithelial growth and branching morph ogenesis induced by aFGF was completely inhibited by an antibody again st aFGF. Heparin caused extra epithelial growth in cooperation with aF GF, but its use resulted in luminal expansion instead of enhanced bran ching. Basic FGF induced abnormal morphogenesis of the epithelium, tho ugh the lumen formed was lined by a simple columnar cell layer. Epider mal growth factor could not maintain epithelial cell growth, and the e pithelium became a smaller and smoother ball than that at the start of cultivation. When covered with a collagen gel instead of Matrigel, th e epithelium remained in its initial form, neither newly branching nor becoming a smooth ball, in the presence of aFGF. These results show t hat the epithelium of lung rudiments was able to branch under mesenchy me-free culture conditions in which a basement membrane matrix and aFG F were substitutes for the mesenchyme.