ACTIVIN DISRUPTS EPITHELIAL BRANCHING MORPHOGENESIS IN DEVELOPING GLANDULAR ORGANS OF THE MOUSE

We report that activin profoundly alters epithelial branching morphoge nesis of embryonic mouse salivary gland, pancreas and kidney rudiments in culture, indicating that it may play a role as a morphogen during mammalian organogenesis. In developing pancreas and salivary gland rud iments, activin causes severe disruption of normal lobulation patterns of the epithelium whereas follistatin, an activin-binding protein, co unteracts the effect of activin. In the kidney, activin delays branchi ng of the ureter bud and reduces the number of secondary branches. TGF -beta induces a pattern of aberrant branching in the ureter bud derive d epithelium distinct from that seen for activin. Reverse-transcriptas e polymerase chain reaction, Northern hybridization and in situ hybrid ization analyses indicate that these developing tissues express the mR NA transcripts for activin subunits, follistatin or activin receptors. Our results are suggestive of a potential role for the activin-follis tatin system as an intrinsic regulator of epithelial branching morphog enesis during mammalian organogenesis.