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Molecular and Cellular Biology, September 2008, p. 5646-5657, Vol. 28, No. 18
0270-7306/08/$08.00+0     doi:10.1128/MCB.00441-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Platelet-Derived Growth Factor Receptors Direct Vascular Development Independent of Vascular Smooth Muscle Cell Function

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas,¹ Heart Failure Research Center, University of Amsterdam, Amsterdam, The Netherlands²

Received 17 March 2008/ Returned for modification 18 April 2008/ Accepted 30 June 2008

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 (PDGFR) and PDGFRβ, we generated embryos that lacked these receptors in cardiomyocytes and vascular smooth muscle cells (VSMC) using conditional gene ablation. Deletion of either PDGFR or PDGFRβ caused no overt vascular defects, but loss of both receptors using an SM22-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.

Published ahead of print on 7 July 2008.