MESENCHYME SPECIFIES EPITHELIAL DIFFERENTIATION IN RECIPROCAL RECOMBINANTS OF EMBRYONIC LUNG AND TRACHEA

Normal lung morphogenesis and cytodifferentiation require interactions between epithelium and mesenchyme, We have previously shown that dist al lung mesenchyme (LgM) is capable of reprogramming tracheal epitheli um (TrE) from day 13-14 rat fetuses to branch in a lung-like pattern a nd express a distal lung epithelial phenotype, In the present study, w e have assessed the effects of tracheal mesenchyme (TrM) on branching and cytodifferentiation of distal lung epithelium (LgE), Tracheae and distal lung tips from day 13 rat fetuses were separated into purified epithelial and mesenchymal components, then recombined as homotypic (L gM + LgE or TrM + TrE) or heterotypic (LgM + TrE or TrM + LgE) recombi nants and cultured for 5 days; unseparated lung tips and tracheae serv ed as controls. Control lung tips, LgM + LgE, and LgM + TrE recombinan ts all branched in an identical pattern. Epithelial cells, including t hose from the induced TrE, contained abundant glycogen deposits and la mellar bodies, and expressed surfactant protein C (SP-C) mRNA. Trachea controls, and both TrM. + TrE, and TrM + LgE recombinants did not bra nch, but instead formed cysts. The epithelium contained ciliated and m ucous secretory cells; importantly, no cells containing lamellar bodie s were observed, nor was SP-C mRNA detected. Mucin immunostaining show ed copious production of mucous in both LgE and TrE when recombined wi th TrM. These results demonstrate that epithelial differentiation in t he recombinants appears to be wholly dependent on the type of mesenchy me used, and that the entire respiratory epithelium has significant pl asticity in eventual phenotype at this stage in development, (C) 1998 Wiley-Liss,Inc.