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Related Experiment Videos

Fibroblast growth factor 18 influences proximal programming during lung morphogenesis.

Jeffrey A Whitsett1, Jean C Clark, Lara Picard

  • 1Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. jeff.whitsett@chmcc.org

The Journal of Biological Chemistry
|April 3, 2002
PubMed
Summary

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Fibroblast growth factor (FGF)-18 directs lung airway development. FGF-18 promotes proximal airway structures while inhibiting peripheral airway formation, revealing its role in lung morphogenesis.

Area of Science:

  • Developmental biology
  • Pulmonary medicine
  • Cell biology

Background:

  • Lung airway structure and function vary significantly along their length.
  • Proximal airways have cartilage and smooth muscle for clearance, while peripheral airways facilitate gas exchange.
  • Factors controlling lung airway cell type and structural differentiation remain largely unknown.

Purpose of the Study:

  • To investigate the role of fibroblast growth factor (FGF)-18 in mediating lung airway development and morphogenesis.
  • To determine how FGF-18 influences the differentiation of proximal versus peripheral airway structures and cell types.

Main Methods:

  • Conditional expression of FGF-18 in epithelial cells of developing mouse lungs.
  • Histological analysis of lung structure, including airway size, cartilage, smooth muscle, and blood vessels.

Related Experiment Videos

  • Analysis of gene and protein expression, including surfactant proteins (SP-B, pro-SP-C).
  • Localization of FGF-18 mRNA in normal mouse lung tissue.

    • Main Results:

    • Conditional FGF-18 expression led to airways adopting proximal airway features.
    • Peripheral lung tubules were reduced, while conducting airways increased in size and extent.
    • Abnormal smooth muscle and cartilage developed in expanded distal airways, with enlarged pulmonary blood vessels.
    • Expression of peripheral lung markers (SP-B, pro-SP-C) was inhibited.
    • FGF-18 mRNA was found in stromal cells near proximal cartilage and in peripheral lung mesenchyme.

    Conclusions:

    • FGF-18 plays a critical role in directing lung morphogenesis by enhancing proximal airway programs.
    • FGF-18 inhibits peripheral lung airway development, demonstrating its dual function in lung structure formation.
    • These findings highlight FGF-18 as a key regulator of differential airway development.