Epidermal growth factor can replace thymic mesenchyme in induction of embryonic thymus morphogenesis in vitro

The thymus is surrounded by a thin layer of mesenchyme and the epithelial-mesenchymal interaction is known to be essential for the thymus development. To clarify the roles of mesenchyme in the thymus lobule formation that occurs around embryonic days 14-15 in vivo, we set up a three-dimensional organ culture system. The epithelium of embryonic day 14 thymic primordium was separated from the mesenchyme and cultured in Matrigel (reconstituted basement membrane). Addition of the mesenchyme to a chamber separated by a membrane filter induced the lobule formation of the thymic epithelium in vitro. We found that epidermal growth factor (EGF) can replace the mesenchyme for lobulation of the embryonic thymus in vitro. Among other growth factors tested, only transforming growth factor (TGF)-alpha was as effective as EGF, in agreement with the fact that EGF and TGF-alpha bind to the same receptor. These results suggest that EGF or its family members may be involved in morphogenesis and differentiation of the thymus gland epithelium, although we cannot exclude the possibility that other unknown factors are required in vivo.