TY - JOUR
T1 - Depletion of FGF acts as a lateral inhibitory factor in lung branching morphogenesis in vitro
AU - Miura, Takashi
AU - Shiota, Kohei
N1 - Funding Information:
The authors especially thank Professor Stuart Newman for critical reading of the manuscript and helpful comments. Helpful discussions with Professor Masayasu Mimura, Professor Hisao Honda, Professor Mitsugu Matsushita, Dr Atsushi Mochizuki, Dr Mikiko Kobayashi-Miura and technical assistance by Dr Hiroyuki Nogawa and Ms Takako Shibayama are also gratefully acknowledged. This work was sponsored by the Japanese Ministry of Education, Culture, Sports, Science and Technology and the Japanese Ministry of Health, Labour and Welfare.
PY - 2002
Y1 - 2002
N2 - Previous studies have shown that the interaction of positive and inhibitory signals plays a crucial role during lung branching morphogenesis. We found that in mesenchyme-free conditions, the lung epithelium exerted a lateral inhibitory effect on the neighbouring epithelium via depletion of fibroblast growth factor 1 (FGF1). Contrary to previous suggestions, bone morphogenetic protein 4 could not substitute for the inhibitory effect. Based on of this observation, we used a reaction-diffusion model of the substrate-depletion type to represent the initial phase of in vitro branching morphogenesis of lung epithelium, with depletion of FGF playing the role of lateral inhibitor. The model was able to account for the effects of the FGF1 concentration, extracellular matrix degradation and different subtypes of FGF on morphogenesis of the lung bud epithelia. These results suggest that the depletion of FGF may be a key regulatory component in initial phase of branching morphogenesis of the lung bud epithelium in vitro.
AB - Previous studies have shown that the interaction of positive and inhibitory signals plays a crucial role during lung branching morphogenesis. We found that in mesenchyme-free conditions, the lung epithelium exerted a lateral inhibitory effect on the neighbouring epithelium via depletion of fibroblast growth factor 1 (FGF1). Contrary to previous suggestions, bone morphogenetic protein 4 could not substitute for the inhibitory effect. Based on of this observation, we used a reaction-diffusion model of the substrate-depletion type to represent the initial phase of in vitro branching morphogenesis of lung epithelium, with depletion of FGF playing the role of lateral inhibitor. The model was able to account for the effects of the FGF1 concentration, extracellular matrix degradation and different subtypes of FGF on morphogenesis of the lung bud epithelia. These results suggest that the depletion of FGF may be a key regulatory component in initial phase of branching morphogenesis of the lung bud epithelium in vitro.
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U2 - 10.1016/S0925-4773(02)00132-6
DO - 10.1016/S0925-4773(02)00132-6
M3 - Article
C2 - 12128203
AN - SCOPUS:0035996954
SN - 0925-4773
VL - 116
SP - 29
EP - 38
JO - Cell Differentiation and Development
JF - Cell Differentiation and Development
IS - 1-2
ER -