TY - JOUR
T1 - Fibroblast growth factor interactions in the developing lung
AU - Lebeche, Djamel
AU - Malpel, Sarah
AU - Cardoso, Wellington V.
N1 - Funding Information:
We would like to thank Drs Jerome Brody and Mary Williams for helpful discussions and critical reading of the manuscript and Dr Maria Ramirez for the help with the PCR. We are indebted to Dr Andrew P. McMahon (Harvard Biolabs) for making available to us many of the reagents used in this work. We are grateful to SUMITOMO Pharmaceuticals (Osaka-Japan) for providing recombinant FGF-10 in the initial steps of this work. We also would like to thank Kompal Sehgal for excellent technical assistance. This work was supported by a grant from NIH/NHLBI (PO1 HL47049).
PY - 1999/8/1
Y1 - 1999/8/1
N2 - Cellular activities that lead to organogenesis are mediated by epithelial-mesenchymal interactions, which ultimately result from local activation of complex gene networks. Fibroblast growth factor (FGF) signaling is an essential component of the regulatory network present in the embryonic lung, controlling proliferation, differentiation and pattern formation . However, little is known about how FGFs interact with other signaling molecules in these processes. By using cell and organ culture systems, we provide evidence that FGFs, Sonic hedgehog (Shh), bone morphogenetic protein 4 (BMP-4), and TGFβ-1 form a regulatory circuit that is likely relevant for lung development in vivo. Our data show that FGF-10 and FGF-7, important for patterning and growth of the lung bud, are differentially regulated by FGF-1, -2 and Shh. In addition, we show that FGFs regulate expression of Shh, BMP-4 and other FGF family members. Our data support a model in which Shh, TGFβ-1 and BMP-4 counteract the bud promoting effects of FGF-10, and where FGF levels are maintained throughout lung development by other FGFs and Shh. Copyright (C) 1999 Elsevier Science Ireland Ltd.
AB - Cellular activities that lead to organogenesis are mediated by epithelial-mesenchymal interactions, which ultimately result from local activation of complex gene networks. Fibroblast growth factor (FGF) signaling is an essential component of the regulatory network present in the embryonic lung, controlling proliferation, differentiation and pattern formation . However, little is known about how FGFs interact with other signaling molecules in these processes. By using cell and organ culture systems, we provide evidence that FGFs, Sonic hedgehog (Shh), bone morphogenetic protein 4 (BMP-4), and TGFβ-1 form a regulatory circuit that is likely relevant for lung development in vivo. Our data show that FGF-10 and FGF-7, important for patterning and growth of the lung bud, are differentially regulated by FGF-1, -2 and Shh. In addition, we show that FGFs regulate expression of Shh, BMP-4 and other FGF family members. Our data support a model in which Shh, TGFβ-1 and BMP-4 counteract the bud promoting effects of FGF-10, and where FGF levels are maintained throughout lung development by other FGFs and Shh. Copyright (C) 1999 Elsevier Science Ireland Ltd.
KW - Bone morphogenetic proteins
KW - Branching morphogenesis
KW - Epithelial-mesenchymal interactions
KW - Fibroblast growth factors
KW - Lung development
KW - Organogenesis
KW - Pattern formation
KW - Sonic hedgehog
KW - Thyroid transcription factor-1
UR - http://www.scopus.com/inward/record.url?scp=0032803573&partnerID=8YFLogxK
U2 - 10.1016/S0925-4773(99)00124-0
DO - 10.1016/S0925-4773(99)00124-0
M3 - Article
C2 - 10446271
AN - SCOPUS:0032803573
SN - 0925-4773
VL - 86
SP - 125
EP - 136
JO - Mechanisms of Development
JF - Mechanisms of Development
IS - 1-2
ER -