Mesodermal development in mouse embryos mutant for fibronectin.
Three independent mutations were made by homologous recombination in two different regions of the fibronectin (FN) gene; all three appeared to be functional null mutations. The embryonic lethal phenotypes of these mutations were indistinguishable; all three FN mutant strains show mesodermal defects and fail to develop notochord or somites. Nevertheless analysis with lineage markers (Brachyury, sonic hedgehog, Notch-1, and mox-1) showed that both the notochord and the somite lineages were induced at the correct times and places. Furthermore, notochord precursor cells showed extensive cell migration in the absence of FN. However, neither notochord nor somites condensed properly in the absence of FN. These results show that specification of notochordal and somitic mesodermal lineages and significant cell migration are independent of fibronectin but that correct morphogenesis of these structures is FN-dependent.
Georges-Labouesse
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EN
Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
George
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EL
Rayburn
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Hynes
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D000818:Animals; D015415:Biomarkers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005808:Genes, Recessive; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008648:Mesoderm; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000196:embryology; D008819:Mice, Nude; D008822:Mice, Transgenic; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000098908:Brachyury Protein
D015415:Biomarkers; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D005353:Fibronectins; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000098908:Brachyury Protein; C497762:Notch1 protein, mouse; C497763:Notch1 protein, rat