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Updated: Jul 3, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Platelet-derived growth factor receptors direct vascular development independent of vascular smooth muscle cell
Wendy J French1, Esther E Creemers, Michelle D Tallquist
1Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines, Dallas, TX, USA.
Insights
Complete loss of platelet-derived growth factor (PDGF) receptor signaling causes embryonic lethality. PDGF receptors in yolk sac mesothelial cells are crucial for blood vessel maturation, independent of vascular smooth muscle cell roles.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cardiovascular Biology
Background:
- Complete loss of platelet-derived growth factor (PDGF) receptor signaling leads to embryonic lethality around embryonic day 9.5.
- Cardiovascular failure is a common cause of embryonic lethality at this developmental stage.
Purpose of the Study:
- To investigate the combined role of PDGF receptor alpha (PDGFRalpha) and PDGFRbeta in cardiovascular and vascular development.
- To identify the cause of embryonic lethality associated with complete loss of PDGF receptor signaling.
Main Methods:
- Conditional gene ablation of PDGFRalpha and PDGFRbeta in cardiomyocytes and vascular smooth muscle cells (VSMC) using an SM22alpha-Cre transgenic mouse line.
- Analysis of yolk sac blood vessel development, collagen deposition, and MMP-2 activity.
- In vitro allantois cultures to assess PDGF signaling in vessel growth.
Main Results:
- Loss of both PDGFRalpha and PDGFRbeta disrupted yolk sac blood vessel development, primarily affecting yolk sac mesothelial cells.
- Reduced collagen deposition and increased MMP-2 activity were observed.
- PDGF signaling is required for blood vessel growth in vitro.
Conclusions:
- PDGF receptors cooperate in yolk sac mesothelial cells to regulate blood vessel maturation.
- These findings suggest PDGF receptor functions in mesothelial cells are critical for embryonic survival and independent of their roles in VSMC development.
Abstract:
Complete loss of platelet-derived growth factor (PDGF) receptor signaling results in embryonic lethality around embryonic day 9.5, but the cause of this lethality has not been identified. Because cardiovascular failure often results in embryonic lethality at this time point, we hypothesized that a failure in cardiovascular development could be the cause. To assess the combined role of PDGF receptor alpha (PDGFRalpha) and PDGFRbeta, we generated embryos that lacked these receptors in cardiomyocytes and vascular smooth muscle cells (VSMC) using conditional gene ablation. Deletion of either PDGFRalpha or PDGFRbeta caused no overt vascular defects, but loss of both receptors using an SM22alpha-Cre transgenic mouse line led to a disruption in yolk sac blood vessel development. The cell population responsible for this vascular defect was the yolk sac mesothelial cells, not the cardiomyocytes or the VSMC. Coincident with loss of PDGF receptor signaling, we found a reduction in collagen deposition and an increase in MMP-2 activity. Finally, in vitro allantois cultures demonstrated a requirement for PDGF signaling in vessel growth. Together, these data demonstrate that PDGF receptors cooperate in the yolk sac mesothelium to direct blood vessel maturation and suggest that these effects are independent of their role in VSMC development.
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