DEFECTS IN MESODERM, NEURAL-TUBE AND VASCULAR DEVELOPMENT IN MOUSE EMBRYOS LACKING FIBRONECTIN

To examine the role of fibronectin in vivo, we have generated mice in which the fibronectin gene is inactivated. Heterozygotes have one half normal levels of plasma fibronectin, yet appear normal. When homozygo us, the mutant allele causes early embryonic lethality, proving that f ibronectin is required for embryogenesis. However, homozygous mutant e mbryos implant and initiate gastrulation normally including extensive mesodermal movement. Neural folds also form but the mutant embryos sub sequently display shortened anterior-posterior axes, deformed neural t ubes and severe defects in mesodermally derived tissues. Notochord and somites are absent; the heart and embryonic vessels are variable and deformed, and the yolk sac, extraembryonic vasculature and amnion are also defective. These abnormalities can be interpreted as arising from fundamental deficits in mesodermal migration, adhesion, proliferation or differentiation as a result of the absence of fibronectin. The nat ure of these embryonic defects leads to reevaluation of suggested role s for fibronectin during early development based on results obtained i n vitro and in embryos of other species.