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Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis.

Publication ,  Journal Article
Weaver, M; Dunn, NR; Hogan, BL
Published in: Development
June 2000

Morphogenesis of the mouse lung involves reciprocal interactions between the epithelial endoderm and the surrounding mesenchyme, leading to an invariant early pattern of branching that forms the basis of the respiratory tree. There is evidence that Fibroblast growth factor 10 (Fgf10) and Bone Morphogenetic Protein 4 (Bmp4), expressed in the distal mesenchyme and endoderm, respectively, play important roles in branching morphogenesis. To examine these roles in more detail, we have exploited an in vitro culture system in which isolated endoderm is incubated in Matrigel(TM) substratum with Fgf-loaded beads. In addition, we have used a Bmp4(lacZ) line of mice in which lacZ faithfully reports Bmp4 expression. Analysis of lung endoderm in vivo shows a dynamic pattern of Bmp4(lacZ) expression during bud outgrowth, extension and branching. In vitro, Fgf10 induces both proliferation and chemotaxis of isolated endoderm, whether it is derived from the distal or proximal lung. Moreover, after 48 hours, Bmp4(lacZ) expression is upregulated in the endoderm closest to the bead. Addition of 30-50 ng/ml of exogenous purified Bmp4 to the culture medium inhibits Fgf-induced budding or chemotaxis, and inhibits overall proliferation. By contrast, the Bmp-binding protein Noggin enhances Fgf-induced morphogenesis. Based on these and other results, we propose a model for the combinatorial roles of Fgf10 and Bmp4 in branching morphogenesis of the lung.

Duke Scholars

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Published In

Development

DOI

ISSN

0950-1991

Publication Date

June 2000

Volume

127

Issue

12

Start / End Page

2695 / 2704

Location

England

Related Subject Headings

  • Respiratory Mucosa
  • Organ Culture Techniques
  • Morphogenesis
  • Mice, Transgenic
  • Mice, Inbred ICR
  • Mice
  • Mesoderm
  • Lung
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor 10
 

Citation

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Weaver, M., Dunn, N. R., & Hogan, B. L. (2000). Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development, 127(12), 2695–2704. https://doi.org/10.1242/dev.127.12.2695
Weaver, M., N. R. Dunn, and B. L. Hogan. “Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis.Development 127, no. 12 (June 2000): 2695–2704. https://doi.org/10.1242/dev.127.12.2695.
Weaver M, Dunn NR, Hogan BL. Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development. 2000 Jun;127(12):2695–704.
Weaver, M., et al. “Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis.Development, vol. 127, no. 12, June 2000, pp. 2695–704. Pubmed, doi:10.1242/dev.127.12.2695.
Weaver M, Dunn NR, Hogan BL. Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development. 2000 Jun;127(12):2695–2704.
Journal cover image

Published In

Development

DOI

ISSN

0950-1991

Publication Date

June 2000

Volume

127

Issue

12

Start / End Page

2695 / 2704

Location

England

Related Subject Headings

  • Respiratory Mucosa
  • Organ Culture Techniques
  • Morphogenesis
  • Mice, Transgenic
  • Mice, Inbred ICR
  • Mice
  • Mesoderm
  • Lung
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor 10