Emerging pulmonary vasculature lacks fate specification

Margaret A. Schwarz, Lauren Caldwell, Danielle Cafasso, Haihua Zheng

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Lung morphogenesis requires precise coordination between branching morphogenesis and vascularization to generate distal airways capable of supporting respiration at the cell-cell interface. The specific origins and types of blood vessels that initially form in the lung, however, remain obscure. Herein, we definitively show that during the early phases of lung development [i.e., embryonic day (E) 11.5], functional vessels, replete with blood flow, are restricted to the mesenchyme, distal to the epithelium. However, by day E14.5, and in response to epithelial-derived VEGF signals, functional vessels extend from the mesen-chyme to the epithelial interface. Moreover, these vessels reside adjacent to multipotent mesenchymal stromal cells that likely play a regulatory role in this process. As well as and distinct from the systemic vasculature, immunostaining for EphrinB2 and EphB4 revealed that arterial and venous identity is not distinguishable in emergent pulmonary vasculature. Collectively, this study provides evidence that lung vascularization initially originates in the mesen-chyme, distal to the epithelium, and that arterial-venous specification does not exist in the early lung. At a mechanistic level, we show that basilar epithelial VEGF prompts endothelial cells to move toward the epithelium where they undergo morphogenesis during the prolifera-tive, canalicular stage. Thus our findings challenge existing notions of vascular origin and identity during development.

Original languageEnglish (US)
Pages (from-to)L71-L81
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1
StatePublished - Jan 2009


  • Blood flow
  • EphB4
  • EphrinB2
  • Fate specification
  • Lectin
  • Platelet endothelial cell adhesion molecule-1
  • Vascular
  • Vessel

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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