MESODERMAL DEVELOPMENT IN MOUSE EMBRYOS MUTANT FOR FIBRONECTIN

Three independent mutations were made by homologous recombination in t wo different regions of the fibronectin (FN) gene; all three appeared to be functional null mutations. The embryonic lethal phenotypes of th ese mutations were indistinguishable; all three FN mutant strains show mesodermal defects and fail to develop notochord or somites. Neverthe less analysis with lineage markers (Brachyury, sonic hedgehog, Notch-1 , and mox-1) showed that both the notochord and the somite lineages we re induced at the correct times and places. Furthermore, notochord pre cursor cells showed extensive cell migration in the absence of FN. How ever, neither notochord nor somites condensed properly in the absence of FN. These results show that specification of notochordal and semiti c mesodermal lineages and significant cell migration are independent o f fibronectin but that correct morphogenesis of these structures is FN -dependent. (C) 1996 Wiley-Liss, Inc.