Tissue interactions mediate early events in pulmonary vasculogenesis

Area of Science:

• Developmental Biology
• Pulmonary Medicine
• Vascular Biology

Background:

• Pulmonary epithelial branching and maturation are well-studied.
• Mechanisms of pulmonary vascular tree development remain largely unknown.
• Epithelial-mesenchymal interactions regulate lung development.

Purpose of the Study:

• To investigate the role of reciprocal epithelial-mesenchymal interactions in pulmonary vascular development.
• To define the temporal and spatial expression of flk-1 mRNA in the developing rat lung.

Main Methods:

• RT-PCR analysis of flk-1 mRNA expression in fetal and neonatal rat lungs.
• In vitro culture of fetal lung mesenchyme with and without lung epithelium.
• Immunohistochemical analysis of flk-1-positive cells in cultured and in vivo lung tissue.

Main Results:

• Flk-1-positive vascular precursors were present from fetal day 11 through birth.
• Early vascular precursors (fetal days 11-16) were localized in the mesenchyme adjacent to the developing epithelium.
• Lung mesenchyme cultured without epithelium showed significant degeneration and loss of flk-1-positive cells.
• Recombination of mesenchyme with epithelium maintained flk-1-positive cells and mimicked in vivo spatial distribution.

Conclusions:

• This study provides the first detailed temporal and spatial patterns of pulmonary vascularization during early development.
• Reciprocal interactions between pulmonary epithelium and mesenchyme are critical for the growth and maintenance of the developing lung vasculature.
• Flk-1 expression indicates epithelial-mesenchymal signaling is essential for vascular precursor development.