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.

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