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Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis
M Weaver1, N R Dunn, B L Hogan
1Howard Hughes Medical Institute and Department of Cell Biology, Vanderbilt Medical Center, Nashville, TN, USA.
Development (Cambridge, England)
|May 24, 2000
Summary
Fibroblast growth factor 10 (Fgf10) and Bone Morphogenetic Protein 4 (Bmp4) are key regulators of mouse lung branching morphogenesis. This study reveals how Fgf10 promotes lung endoderm growth and migration, while Bmp4 can inhibit these processes.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Lung morphogenesis relies on epithelial-mesenchymal interactions.
- Fibroblast growth factor 10 (Fgf10) and Bone Morphogenetic Protein 4 (Bmp4) are implicated in lung branching.
- Understanding their precise roles is crucial for developmental biology.
Purpose of the Study:
- To investigate the roles of Fgf10 and Bmp4 in mouse lung branching morphogenesis.
- To elucidate the molecular mechanisms underlying lung development.
Main Methods:
- Utilized an in vitro culture system with isolated mouse lung endoderm and Fgf-loaded beads.
- Employed a Bmp4(lacZ) reporter mouse line to track Bmp4 expression in vivo.
- Administered exogenous Bmp4 and Noggin in vitro to assess their effects on Fgf10-induced responses.
Main Results:
- Fgf10 stimulates proliferation and chemotaxis of lung endoderm.
- Bmp4 expression is dynamically regulated during lung development and upregulated by Fgf10 in vitro.
- Exogenous Bmp4 inhibits Fgf10-induced lung endoderm budding and proliferation, while Noggin enhances it.
Conclusions:
- Fgf10 and Bmp4 play combinatorial roles in regulating lung branching morphogenesis.
- A balance between Fgf10 signaling and Bmp4 activity is essential for proper lung development.