Platelet-derived growth factor receptors direct vascular development independent of vascular smooth muscle cell function.
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.
French
Wendy J
WJ
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines, Dallas, TX, USA.
Creemers
Esther E
EE
Tallquist
Michelle D
MD
D000818:Animals; D001808:Blood Vessels / Q000033:anatomy & histology / Q000502:physiology; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D004848:Epithelium / Q000033:anatomy & histology / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015017:Yolk Sac / Q000098:blood supply / Q000502:physiology
D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta