Chimera analysis reveals that fibroblasts and endothelial cells require platelet-devived growth factor receptor beta expression for participation in reactive connective tissue formation in adults but not during development

The hypothesis that platelet-derived growth factor (PDGF) plays an importan t role in repair of connective tissue has been difficult to test experiment ally, in part because the disruption of any of the PDGF ligand and receptor genes is embryonic lethal. The have developed a method that circumvents th e embryonic lethality of the PDGF receptor (R)beta-/- genotype and minimize s the tendency of compensatory processes to mask the phenotype of gene disr uption by comparing the behavior of wild-type and PDGFR beta-/- cells withi n individual chimeric mice. This quantitative chimera analysis method has r evealed that during development PDGFR beta expression is important for all muscle lineages but not for fibroblast or endothelial lineages, Here we rep ort that fibroblasts and endothelial cells, but not leukocytes, are depende nt on PDGFR beta expression during the formation of new connective tissue i n and around sponges implanted under the skin. Even the 50% reduction in PD GFR beta gene dosage in PDGEE beta+/- cells reduces fibroblast and endothel ial cell participation by 85%. These results demonstrate that the PDGFR bet a/PDGF B-chain system plays an important direct role in driving both fibrob last and endothelial cell participation in connective tissue repair, that c ell behavior can be regulated by relatively small, changes in PDGFR beta ex pression, and that the functions served by PDGF in wound healing are differ ent from the roles served during development.