Signaling to the epithelium is not sufficient to mediate all of the effects of transforming growth factor beta and bone morphogenetic protein 4 on murine embryonic lung development
Ad. Bragg et al., Signaling to the epithelium is not sufficient to mediate all of the effects of transforming growth factor beta and bone morphogenetic protein 4 on murine embryonic lung development, MECH DEVEL, 109(1), 2001, pp. 13-26
Many studies have suggested that transforming growth factor beta (TGF-beta)
and bone morphogenetic protein 4 (Bmp4) regulate early development of the
lung. In this study, administration of growth factors directly into the lum
en of lungs grown in organ culture was used to limit their activity to the
epithelium and test the hypothesis that signaling to the epithelium is suff
icient to mediate the known effects of TGF-beta and BMP-4 on early lung dev
elopment. Addition of TGF-beta1, beta2, or beta3 to the medium surrounding
lungs grown in organ culture resulted in decreased branching, reduced cell
proliferation, accumulation of alpha -smooth muscle actin protein (alpha -S
MA) in the mesenchyme, and decreased expression of a marker for respiratory
epithelium, surfactant protein-C (Sp-C). When TGF-beta1 was restricted to
the epithelium, accumulation of alpha -SMA and inhibition of Sp-C expressio
n were not observed but branching and proliferation were inhibited. In cont
rast, branching was not inhibited in lungs where TGF-beta2 or TGF-beta3 wer
e restricted to the epithelium suggesting differences in the mechanism of s
ignaling by TGF-beta1, TGF-beta2 or TGF-beta3 in lung. Addition of Bmp4 to
the medium surrounding lungs grown in organ culture stimulated cell prolife
ration and branching morphogenesis; however, direct injection of Bmp4 into
the lung lumen had no effect on proliferation or branching, Based on these
data and data from mesenchyme-free cultures, we propose that the mesenchyme
influences growth factor signaling in the lung. (C) 2001 Elsevier Science
Ltd. All rights reserved.