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Mesodermal deletion of transforming growth factor-beta receptor II disrupts lung epithelial morphogenesis: cross-talk

Min Li1, Changgong Li, Yi-hsin Liu

  • 1Division of Neonatology, Department of Pediatrics, Will Rogers Institute Pulmonary Research Center, University of Southern California School of Medicine, Los Angeles, CA 90093, USA.

The Journal of Biological Chemistry
|November 8, 2008
PubMed

Insights

Transforming growth factor-beta (TGF-beta) signaling in embryonic lung mesenchyme modulates Sonic hedgehog (Shh) pathway activity. This study provides the first in vivo evidence of reciprocal cross-communication between these critical developmental pathways.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Sonic hedgehog (Shh) and transforming growth factor-beta (TGF-beta) signaling pathways are crucial for vertebrate embryonic development.
  • In vitro studies suggest potential interactions between Shh and TGF-beta pathways, but in vivo evidence during development is lacking.

Purpose of the Study:

  • To investigate in vivo interactions between Shh and TGF-beta signaling during embryonic lung morphogenesis.
  • To determine if TGF-beta receptor signaling in the mesenchyme influences Shh pathway transduction.

Main Methods:

  • Generation of transgenic mice with mesodermal-specific deletion of the type II TGF-beta receptor (TbetaRII).
  • Analysis of embryonic lung development, including cartilage formation and epithelial branching morphogenesis.
  • Quantitative analysis of Shh signaling pathway components (Patched, Gli-1) and Shh ligand levels.

Main Results:

  • Mesodermal-specific deletion of TbetaRII led to embryonic lethality and severe lung abnormalities, including defective cartilage and epithelial branching.
  • Cystic airway malformations were observed due to impaired epithelial morphogenesis.
  • Deletion of mesenchymal TbetaRII upregulated downstream Shh targets (Patched, Gli-1) without altering epithelial Shh ligand levels.

Conclusions:

  • TGF-beta receptor-mediated signaling in lung mesenchyme is essential for modulating Shh pathway transduction originating from the epithelium.
  • This study provides the first in vivo evidence of a reciprocal cross-communication mechanism between Shh and TGF-beta pathways during embryonic development.

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