Adenoviral-mediated expression of antisense RNA to fibroblast growth factors disrupts murine vascular development

Fibroblast growth factors (FGFs) are expressed in the developing embryo and are postulated to regulate embryonic and vascular growth. The goal of this study was to elucidate the role of basic fibroblast growth factor (FGF-2) in early murine embryonic cardiovascular development in the mouse embryo. G estation day 7.5 embryos were harvested and placed in culture, and 12 hr la ter replication-defective adenovirus (0.5 x 10(6) plaque forming units) enc oding either beta-galactosidase or antisense FGF-2 RNA was injected into th e sinus venosus of the cultured embryos. Embryos receiving only replication -defective adenovirus expressing the beta-galactosidase gene continued to d evelop normally over the next 12 hr, In contrast, those receiving adenoviru s encoding antisense FGF-2 RNA displayed marked morphogenetic abnormalities , including cessation of growth and abnormal yolk sac vascular development, even though the embryonic hearts continued to beat. Abnormal development o f the yolk sac vasculature was confirmed by microangiography and by histolo gic examination. Coinjection of virus carrying FGF-2 cDNA in the sense orie ntation reversed the effects of antisense FGF-2 RNA expression. These resul ts confirm the efficacy of the replication-defective adenovirus for targeti ng gene expression to the developing vasculature and provide evidence for a critical role of FGF in the normal vascular assembly in the early embryo. Cessation of embryonic growth on expression of antisense FGF-2 RNA was most likely attributable to failure of efficient circulation of the early embry onic blood cells from the yolk sac into the embryo. Dev. Dyn. 1998;213:421- 430. (C) 1998 Wiley-Liss, Inc.