Emerging pulmonary vasculature lacks fate specification

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Lung
Morphogenesis
Epithelium
Vascular Endothelial Growth Factor A
Blood Vessels
Cell Respiration
Mesoderm
Mesenchymal Stromal Cells
Embryonic Development
Endothelial Cells

Keywords

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

ASJC Scopus subject areas

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

Cite this

Emerging pulmonary vasculature lacks fate specification. / Schwarz, Margaret A.; Caldwell, Lauren; Cafasso, Danielle; Zheng, Haihua.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 296, No. 1, 01.2009.

Research output: Contribution to journalArticle

Schwarz, Margaret A. ; Caldwell, Lauren ; Cafasso, Danielle ; Zheng, Haihua. / Emerging pulmonary vasculature lacks fate specification. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2009 ; Vol. 296, No. 1.
@article{052bb4fd777c43fda640ab1810978941,
title = "Emerging pulmonary vasculature lacks fate specification",
abstract = "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.",
keywords = "Blood flow, EphB4, EphrinB2, Fate specification, Lectin, Platelet endothelial cell adhesion molecule-1, Vascular, Vessel",
author = "Schwarz, {Margaret A.} and Lauren Caldwell and Danielle Cafasso and Haihua Zheng",
year = "2009",
month = "1",
doi = "10.1152/ajplung.90452.2008",
language = "English (US)",
volume = "296",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Emerging pulmonary vasculature lacks fate specification

AU - Schwarz, Margaret A.

AU - Caldwell, Lauren

AU - Cafasso, Danielle

AU - Zheng, Haihua

PY - 2009/1

Y1 - 2009/1

N2 - 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.

AB - 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.

KW - Blood flow

KW - EphB4

KW - EphrinB2

KW - Fate specification

KW - Lectin

KW - Platelet endothelial cell adhesion molecule-1

KW - Vascular

KW - Vessel

UR - http://www.scopus.com/inward/record.url?scp=58149529359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149529359&partnerID=8YFLogxK

U2 - 10.1152/ajplung.90452.2008

DO - 10.1152/ajplung.90452.2008

M3 - Article

VL - 296

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1

ER -