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Related Experiment Videos

Heparan sulfate-FGF10 interactions during lung morphogenesis.

Konstantin I Izvolsky1, Deana Shoykhet, Yu Yang

  • 1Pulmonary Center, Department of Medicine, Boston University School of Medcine, MA 02118, USA.

Developmental Biology
|June 5, 2003
PubMed
Summary

Heparan sulfates (HS) modulate fibroblast growth factor 10 (FGF10) signaling crucial for lung development. Specific O-sulfated HS patterns in the lung mesenchyme and epithelium are essential for FGF10-mediated lung bud formation.

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Fibroblast growth factor 10 (FGF10) signaling via FGFR2b is vital for lung development.
  • Heparan sulfates (HS) are known modulators of growth factor signaling, but their role in vertebrate lung development is unclear.

Purpose of the Study:

  • To map HS expression in the developing lung.
  • To investigate how HS interactions with FGF10-FGFR2b influence lung morphogenesis.
  • To elucidate the role of HS sulfation patterns in FGF10-mediated lung budding.

Main Methods:

  • Mapping of HS expression in embryonic lungs.
  • Analysis of HS-FGF10-FGFR2b interactions using embryonic lung cultures.
  • Experiments with selectively sulfated heparins.

Related Experiment Videos

  • Assessment of gene expression and lung pattern formation.
  • Main Results:

    • Specific O-sulfated HS are dynamically expressed in the lung mesenchyme near Fgf10 expression.
    • Highly sulfated HS are found in the basement membranes of branching epithelial tubules.
    • Disrupting HS gradients or altering HS sulfation impairs FGF10 signaling and lung pattern formation.
    • O-sulfated HS groups are critical for FGF10 signaling activation during lung bud formation.

    Conclusions:

    • Developmentally regulated regional patterns of HS sulfation critically influence FGF10's ability to induce lung budding.
    • HS 6-O-sulfotransferase expression is localized to the tips of branching tubules.
    • HS sulfation patterns are essential for FGF10-mediated lung morphogenesis.