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Publication : Platelet-derived growth factor receptors direct vascular development independent of vascular smooth muscle cell function.

First Author  French WJ Year  2008
Journal  Mol Cell Biol Volume  28
Issue  18 Pages  5646-57
PubMed ID  18606782 Mgi Jnum  J:140245
Mgi Id  MGI:3813161 Doi  10.1128/MCB.00441-08
Citation  French WJ, et al. (2008) Platelet-derived growth factor receptors direct vascular development independent of vascular smooth muscle cell function. Mol Cell Biol 28(18):5646-57
abstractText  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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