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JOURNAL ARTICLES
Mesodermal defects and cranial neural crest apoptosis in alpha5 integrin-null embryos
K.L. Goh, J.T. Yang, R.O. Hynes
Development 1997 124: 4309-4319;

Summary

Alpha5beta1 integrin is a cell surface receptor that mediates cell-extracellular matrix adhesions by interacting with fibronectin. Alpha5 subunit-deficient mice die early in gestation and display mesodermal defects; most notably, embryos have a truncated posterior and fail to produce posterior somites. In this study, we report on the in vivo effects of the alpha5-null mutation on cell proliferation and survival, and on mesodermal development. We found no significant differences in the numbers of apoptotic cells or in cell proliferation in the mesoderm of alpha5-null embryos compared to wild-type controls. These results suggest that changes in overall cell death or cell proliferation rates are unlikely to be responsible for the mesodermal deficits seen in the alpha5-null embryos. No increases in cell death were seen in alpha5-null embryonic yolk sac, amnion and allantois compared with wild-type, indicating that the mutant phenotype is not due to changes in apoptosis rates in these extraembryonic tissues. Increased numbers of dying cells were, however, seen in migrating cranial neural crest cells of the hyoid arch and in endodermal cells surrounding the omphalomesenteric artery in alpha5-null embryos, indicating that these subpopulations of cells are dependent on alpha5 integrin function for their survival. Mesodermal markers mox-1, Notch-1, Brachyury (T) and Sonic hedgehog (Shh) were expressed in the mutant embryos in a regionally appropriate fashion. Both T and Shh, however, showed discontinuous expression in the notochords of alpha5-null embryos due to (1) degeneration of the notochordal tissue structure, and (2) non-maintenance of gene expression. Consistent with the disorganization of notochordal signals in the alpha5-null embryos, reduced Pax-1 expression and misexpression of Pax-3 were observed. Anteriorly expressed HoxB genes were expressed normally in the alpha5-null embryos. However, expression of the posteriormost HoxB gene, Hoxb-9, was reduced in alpha5-null embryos. These results suggest that alpha5beta1-fibronectin interactions are not essential for the initial commitment of mesodermal cells, but are crucial for maintenance of mesodermal derivatives during postgastrulation stages and also for the survival of some neural crest cells.

REFERENCES

    1. Adams J. C.,
    2. Watt F. M.
    (1990) Changes in keratinocyte adhesion during terminal differentiation: reduction in fibronectin binding precedesloss from the cell surface. Cell 63, 425–435
    OpenUrlCrossRefPubMedWeb of Science
    1. Adams J. C.,
    2. Watt F. M.
    (1993) Regulation of development and differentiation by the extracelullar matrix. Development 117, 1183–1198
    OpenUrlPubMedWeb of Science
    1. Akiyama S. K.,
    2. Yamada S. S.,
    3. Chen W. T.,
    4. Yamada K.
    (1989) Anaylsis of fibronectin receptor function with monoclonal antibodies: roles in cell adhesion, migration matrix assembly and cytoskeletal organization. J. Cell Biol 109, 863–875
    OpenUrlAbstract/FREE Full Text
    1. Beauvais A.,
    2. Erickson C. A.,
    3. Goins T.,
    4. Craig S. E.,
    5. Humphries M. J.,
    6. Theiry J.-P.,
    7. Dufour S.
    (1995) Changes in the fibronectin-specific integrin expression pattern modify the migratory behavior in the embryonic environment. J. Cell Biol 128, 699–713
    OpenUrlAbstract/FREE Full Text
    1. Beddington R. S. P.,
    2. Rashbass P.,
    3. Wilson V.
    (1992) Brachyury—a gene affecting mouse gastrulation and early organogenesis. Development 1992, 157–165
    1. Bober E.,
    2. Franz T.,
    3. Arnold H.,
    4. Gruss P.,
    5. Tremblay P.
    (1994) Pax-3 is required for the development of limb muscles: a possible role for the migration of dermomyotomal muscle progenitor cells. Development 120, 603–612
    OpenUrlAbstract
    1. Boukamp P.,
    2. Fusenig N. E.
    (1993) ‘Trans-differentiation’ from epidermal to mesenchymal/myogenic phenotype is associated with a drastic change in cell-cell and cell-matrix adhesion meolecules. J. Cell Biol 120, 981–993
    OpenUrlAbstract/FREE Full Text
    1. Candia A. F.,
    2. Hu J.,
    3. Crosby J.,
    4. Lalley P. A.,
    5. Noden D.,
    6. Na deau J. H.,
    7. Wright C. VE.
    (1992) Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development 116, 1123–1136
    OpenUrlAbstract/FREE Full Text
    1. Chang D. T.,
    2. Lopez A.,
    3. Kessler D. P.,
    4. Chiang C.,
    5. Simandl B. K.,
    6. Zhao R.,
    7. Seldin M. F.,
    8. Fallon J.,
    9. Beachy P. A.
    (1994) Products, genetic linkage and limb patterning activity of a murine hedgehog gene. Development 120, 3339–3353
    OpenUrlAbstract
    1. Clark E. A.,
    2. Brugge J. S.
    (1995) Integrins and signal transduction pathways: the road taken. Science 268, 233–239
    OpenUrlAbstract/FREE Full Text
    1. Conlon R. A.,
    2. Rossant J.
    (1992) Exogenous retinoic acid induces anterior ectopic expression of murine Hox-2 genes in vivo. Development 116, 357–368
    OpenUrlAbstract/FREE Full Text
    1. Conlon R. A.,
    2. Reaume A. G.,
    3. Rossant J.
    (1995) Notch1 is required for the coordinate segmentation of somites. Development 121, 1533–1545
    OpenUrlAbstract
    1. Damsky C. H.,
    2. Werb Z.
    (1992) Signal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information. Curr. Opin. Cell Biol 4, 772–781
    OpenUrlCrossRefPubMed
    1. Dedhar S.
    (1995) Integrin mediated signal transduction in oncogenesis: an overview. Cancer Metastasis Rev 14, 165–172
    OpenUrlCrossRefPubMedWeb of Science
    1. Del Amo F. F.,
    2. Smith D. E.,
    3. Swiatek P.,
    4. Gendron-Maguire M.,
    5. Greenspan R. J.,
    6. MacMachon A. P.,
    7. Gridley T.
    (1992) Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development. Development 115, 737–744
    OpenUrlAbstract/FREE Full Text
    1. DeSimone D. W.
    (1994) Adhesion and matrix in vertebrate development. Curr. Opin. Cell Biol 6, 747–51
    OpenUrlCrossRefPubMedWeb of Science
    1. Deutsch U.,
    2. Dressler G. R.,
    3. Gruss P.
    (1988) Pax-1, a member of a pair box homologous murine gene family, is expressed in segmented structures during development. Cell 53, 617–625
    OpenUrlCrossRefPubMedWeb of Science
    1. Erickson C. A.,
    2. Perris R.
    (1993) The role of cell-cell and cell-matrix interactions in the morphogenesis of the neural crest. Dev. Biol 159, 60–74
    OpenUrlCrossRefPubMedWeb of Science
    1. Fan C.,
    2. Tessier-Lavigne M.
    (1994) Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog. Cell 79, 1175–1186
    OpenUrlCrossRefPubMedWeb of Science
    1. Foggerty F. J.,
    2. Akiyama S. K.,
    3. Yamada K. M.,
    4. Mosher D. F.
    (1990) Inhibition of binding of fibronectin to matrix assmebly sites by anti-integrin () antibodies. J. Cell Biol 111, 699–708
    OpenUrlAbstract/FREE Full Text
    1. Gavrieli Y.,
    2. Sherman Y.,
    3. Ben-Sasson S. A.
    (1992) Identification of programmed cell death in situ via specific labelling of nuclear DNA fragmentation. J. Cell Biol 119, 493–501
    OpenUrlAbstract/FREE Full Text
    1. George E. L.,
    2. Georges-Labouesse E. N.,
    3. Patel-King R. S.,
    4. Rayburn H.,
    5. Hynes R. O.
    (1993) Defects in mesoderm, neural tube and vasacular development in mouse embryos lacking fibronectin. Development 119, 1079–1091
    OpenUrlAbstract
    1. Giancotti F. G.,
    2. Ruoslahti E.
    (1990) Elevated levels of thefibronectin receptor suppress the transformed phenotype of chinese hamster ovary cells. Cell 60, 849–859
    OpenUrlCrossRefPubMedWeb of Science
    1. Goulding M. D.,
    2. Chalepakis G.,
    3. Deutsch U.,
    4. Erselius J. R.,
    5. Gruss P.
    (1991) Pax-3, a novel murine DNA-binding protein expressed during early neurogenesis. EMBO J 10, 1135–1147
    OpenUrlPubMedWeb of Science
    1. Graham A.,
    2. Heyman I.,
    3. Lumsden A.
    (1993) Even-numbered rhombomeres control the apoptotic elimination of neural crest cells from odd-numbered rhombomeres in the chick hindbrain. Development 119, 233–245
    OpenUrlAbstract
    1. Herrmann B. G.
    (1991) Expression pattern of the Brachyury gene in whole-mount Twis/Twis mutant embryos. Development 113, 913–.
    OpenUrlAbstract
    1. Holland P. W. H.,
    2. Hogan B. L. M.
    (1988) Expression of homeobox genes during mouse development: a review. Genes Dev 2, 773–782
    OpenUrlFREE Full Text
    1. Huhtala P.,
    2. Humphries M. J.,
    3. McCarthy J. B.,
    4. Tremble P. M.,
    5. Werb A.,
    6. Damsky C.
    (1995) Cooperative signaling byand integrins regulates metalloproteinase gene expression in fibroblasts adhering to fibronectin. J. Cell Biol 129, 867–879
    OpenUrlAbstract/FREE Full Text
    1. Hynes R. O.
    (1992) Integrins: versatility, modulation, and signalling in cell adhesion. Cell 69, 11–23
    OpenUrlCrossRefPubMedWeb of Science
    1. Jeffs P.,
    2. Jaques K.,
    3. Osmond M.
    (1992) Cell death in cranial neural crest development. Anat Embryol 185, 583–588
    OpenUrlPubMed
    1. Johnson R. L.,
    2. Laufer E.,
    3. Riddle R. D.,
    4. Tabin C.
    (1994) Ectopic expression of sonic hedgehog alters dorsal-ventral patterning of somites. Cell 79, 1165–1173
    OpenUrlCrossRefPubMedWeb of Science
    1. Kessel M.,
    2. Gruss P.
    (1990) Murine developmental control genes. Science 249, 374–379
    OpenUrlAbstract/FREE Full Text
    1. Morgenbesser S. D.,
    2. Schreiber-Agus N.,
    3. Bidder M.,
    4. Mahon K.A.,
    5. Overbeek P. A.,
    6. Horner J.,
    7. DePinho R.A.
    (1995) Contrasting roles for c-Myc and L-Myc in the regulation of cellular growth and differentiation in vivo. EMBO J 14, 743–796
    OpenUrlPubMedWeb of Science
    1. Muschuler J. L.,
    2. Horwitz A. F.
    (1991) Down-regulation of the chickenintegrin fibronectin receptor during development. Development 113, 327–337
    OpenUrlAbstract
    1. Placzek M.,
    2. Jessell T. M.,
    3. Dodd J.
    (1993) Induction of floorplate differentiation by contact-dependent, homeogenetic signals. Development 117, 205–218
    OpenUrlAbstract/FREE Full Text
    1. Schwartz M. A.,
    2. Schaller M. D.,
    3. Ginsberg M. H.
    (1995) Integrins: Emerging paradigms of signal transduction. Annu. Rev. Cell Dev. Biol 11, 549–599
    OpenUrlCrossRefPubMedWeb of Science
    1. Stoner C.,
    2. Gudas L. J.
    (1989) Mouse cellular retinoic acid binding protein: cloning, complementary DNA sequence, and messenger RNA expression during the retinoic acid-induced differentiation of F9 wildtype and RA-3-10 mutant teratocarcinoma cells. Cancer Research 49, 1497–1504
    OpenUrlAbstract/FREE Full Text
    1. Tam P. L.,
    2. Trainor P. A.
    (1994) Specification and segmentation of the paraxial mesoderm. Anat Embryol 189, 275–305
    OpenUrlPubMed
    1. Varner J. A.,
    2. Emerson D. A.,
    3. Juliano R. L.
    (1995) Integrinexpression negatively regulates growth: reversal by attachment to fibronectin. Mol. Biol. Cell 6, 725–740
    OpenUrlAbstract/FREE Full Text
    1. White K.,
    2. Grether M. E.,
    3. Abrams J. M.,
    4. Young L.,
    5. Farrell K.,
    6. Steller H.
    (1994) Genetic control of programmed cell death in Drosophila. Science 264, 677–683
    OpenUrlAbstract/FREE Full Text
    1. Wilson V.,
    2. Rashbass P.,
    3. Beddington R. S. P.
    (1993) Chimeric analysis of T (Brachyury) gene function. Development 117, 1321–1331
    OpenUrlAbstract
    1. Yang J. T.,
    2. Hynes R. O.
    (1996) Fibronectin receptor functions in embryonic cells deficient inintegrin can be replaced by vintegrins. Mol. Biol. Cell 7, 1937–1748
    OpenUrl
    1. Yang J. T.,
    2. Rayburn H.,
    3. Hynes R. O.
    (1993) Embryonic mesodermal defects inintegrin-deficient mice. Development 119, 1093–1105
    OpenUrlAbstract
    1. Yang J. T.,
    2. Rayburn H.,
    3. Hynes R. O.
    (1995) Cell adhesion events mediated byintegrins are essential in placental and cardia development. Development 121, 549–560
    OpenUrlAbstract
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JOURNAL ARTICLES
Mesodermal defects and cranial neural crest apoptosis in alpha5 integrin-null embryos
K.L. Goh, J.T. Yang, R.O. Hynes
Development 1997 124: 4309-4319;
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