Evidence of interlobular repulsion during branching morphogenesis in mouse salivary glands.

We developed a culture method for detecting repulsion among epithelial lobules during branching morphogenesis in mouse submandibular glands. Three epithelia were placed at each vertex of an imaginary triangle apart but near enough to meet with one another if each of them expands radially during the culture period. No repulsion was observed following cultivation with neuregulin 1 and lysophosphatidic acid; the epithelia actively branched and nearly contacted one another in the triangle's center. In contrast, strong repulsion was observed among the epithelia cultured with fibroblast growth factor 1 (FGF1), which exhibited less branching and moved away from the center. The localization of DiI- (1,1', di-octadecyl-3,3,3',3',-tetramethylindo-carbocyanine perchlorate) and BrdU- (5-bromodeoxyuridine) labeled cells in the cultures exposed to FGF1 indicated that the cells were unable to move and proliferate in the center. SB431542, an inhibitor of transforming growth factor-beta (TGFbeta) signaling, was unable to abolish this repulsion, suggesting that TGFbetas will not probably act as repellants in this case.