title: α5β1 integrin-mediated adhesion to fibronectin is required for axis elongation and somitogenesis in mice.
abstract: The arginine-glycine-aspartate (RGD) motif in fibronectin (FN) represents the major binding site for α5β1 and αvβ3 integrins. Mice lacking a functional RGD motif in FN (FN(RGE/RGE)) or α5 integrin develop identical phenotypes characterized by embryonic lethality and a severely shortened posterior trunk with kinked neural tubes. Here we show that the FN(RGE/RGE) embryos arrest both segmentation and axis elongation. The arrest is evident at about E9.0, corresponding to a stage when gastrulation ceases and the tail bud-derived presomitic mesoderm (PSM) induces α5 integrin expression and assumes axis elongation. At this stage cells of the posterior part of the PSM in wild type embryos are tightly coordinated, express somitic oscillator and cyclic genes required for segmentation, and form a tapered tail bud that extends caudally. In contrast, the posterior PSM cells in FN(RGE/RGE) embryos lost their tight associations, formed a blunt tail bud unable to extend the body axis, failed to induce the synchronised expression of Notch1 and cyclic genes and cease the formation of new somites. Mechanistically, the interaction of PSM cells with the RGD motif of FN is required for dynamic formation of lamellipodia allowing motility and cell-cell contact formation, as these processes fail when wild type PSM cells are seeded into a FN matrix derived from FN(RGE/RGE) fibroblasts. Thus, α5β1-mediated adhesion to FN in the PSM regulates the dynamics of membrane protrusions and cell-to-cell communication essential for elongation and segmentation of the body axis.
authors.affiliation: Departament de Bioquimica i Biologia Molecular, Universitat de València, Burjassot, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Girós
authors.forename: Katja
authors.initials: K
authors.lastname: Grgur
authors.forename: Achim
authors.initials: A
authors.lastname: Gossler
authors.forename: Mercedes
authors.initials: M
authors.lastname: Costell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D047108:Embryonic Development / Q000235:genetics; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009842:Oligopeptides; D011485:Protein Binding; D019030:Receptors, Vitronectin / Q000378:metabolism*; D019170:Somites / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism
chemical_list: D005353:Fibronectins; D009842:Oligopeptides; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; C047981:arginyl-glycyl-aspartic acid