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 homozygous, the mutant allele causes early embryonic lethality, proving that fibronectin is required for embryogenesis. However, homozygous mutant embryos implant and initiate gastrulation normally including extensive mesodermal movement. Neural folds also form but the mutant embryos subsequently display shortened anterior-posterior axes, deformed neural tubes 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 nature of these embryonic defects leads to reevaluation of suggested roles for fibronectin during early development based on results obtained in vitro and in embryos of other species.

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