Integrins During Development

  • Donald Gullberg
  • Peter Ekblom


Virtually every developing cell encounters some form of extracellular matrix (ECM) and through the years data have accumulated on the importance of these interactions for the development of the organism.1,2 These data have been collected through in vitro experiments with isolated cells, studies of organ cultures or developing organisms. Explicit functions have been inferred from inhibition experiments with antibodies and peptides, translational blockade with antisense oligonucleotides, from analyses of naturally occurring mutations, and more recently, from truncations, mutations and deletions in the genes coding for selected proteins.


Focal Adhesion Kinase Muscular Dystrophy Muscle Development Epidermolysis Bullosa Integrin Subunit 
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  1. 1.
    Adams J, Watt FM. Regulation of development and differentiation by the extracellular matrix. Development 1993; 117: 1183 - 1198.PubMedGoogle Scholar
  2. 2.
    Hay ED. Extracellular matrix alters epithelial differentiation. Curr Opin Cell Biol 1993; 5: 1029 - 1035.CrossRefPubMedGoogle Scholar
  3. 3.
    Ruoslahti E. Fibronectin and its receptor. Annu Rev Biochem 1988; 4: 229 - 255.Google Scholar
  4. 4.
    Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992; 69: 11 - 25.CrossRefPubMedGoogle Scholar
  5. 5.
    Almeida EAC, Huovila APJ, Sutherland AE et al. Mouse egg integrin a(f3i function as a sperm receptor. Cell 1995; 81: 1095 - 1104.CrossRefPubMedGoogle Scholar
  6. 6.
    Fässler R, Meyer M. Consequences of lack of (31 integrin gene expression in mice. Genes Dev 1995; 9: 1896 - 1908.CrossRefPubMedGoogle Scholar
  7. 7.
    Stephens LE, Sutherland AE, Klimanskaya IV et al. Deletion of f31 integrin in mice results in inner cell mass failure and periimplantation lethality. Genes Dev 1995; 9: 1883 - 1895.CrossRefPubMedGoogle Scholar
  8. 8.
    Fässler R, Pfaff M, Murphy J et al. Lack of ß1 integrin gene in embryonic stem cells affects morphology, adhesion and migration but not integration into the inner cell mass of blastocysts. J Cell Biol 1994; 128: 979 - 988.CrossRefGoogle Scholar
  9. 9.
    Wennerberg K, Lohikangas L, Gullberg D et al. 131 integrin-dependent and-independent polymerization of fibronectin. J Cell Biol 1996; 132: 227 - 238.CrossRefPubMedGoogle Scholar
  10. 10.
    Hirsch E, Iglesias A, Potocnik AJ et al. Impaired migration but not differentiation of haematopoitic stem cells in the absence of ß1 integrins. Nature 1996; 380: 171 - 175.CrossRefPubMedGoogle Scholar
  11. 11.
    Languino LR, Ruoslahti E. An alternative form of the beta 1 subunit with a variant cytoplasmic domain. J Biol Chem 1992; 267: 7116 - 7120.PubMedGoogle Scholar
  12. 12.
    Balzac F, Belkin AM, Koteliansky VE et al. Expression and functional analysis of a cytoplasmic domain variant of the 131 integrin subunit. J Cell Biol 1993; 121: 171 - 178.CrossRefPubMedGoogle Scholar
  13. 13.
    Meredith J, Takada Y, Fornaro M et al. Inhibition of cell cycle progression by the alternatively spliced integrin Pic. Science 1995; 269: 1570 - 1572.CrossRefPubMedGoogle Scholar
  14. 14.
    van der Flier A, Kuleman I, Baudoin C et a1. A novel f31 integrin isoform produced by alternative splicing: unique expression in cardiac and skeletal muscle. FEBS Lett 1995; 369: 340 - 344.CrossRefPubMedGoogle Scholar
  15. 15.
    Zhidkova NI, Belkin AM, Mayne R. Novel isoform of f31 integrin expressed in skeletal and cardiac muscle. Biochem Biophys Res Comm 1995; 241: 279 - 285.CrossRefGoogle Scholar
  16. 16.
    Tarone G, Balzac F, Brancaccio M et al. 131D, a muscle specific integrin isoform generated by alternative splicing of the cytoplasmic domain. Abstract Kestone meeting on Molecular and Developmental biology of the extracellular matrix. 1996.Google Scholar
  17. 17.
    Belkin A, Zhidkova NI, Balzac F et al. [31D integrin displaces the 131A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells. J Cell Biol 1996; 132: 211 - 226.CrossRefPubMedGoogle Scholar
  18. 18.
    Collo G, Starr L, Quaranta V. A new isoform of the laminin receptor 07[31 is developmentally regulated in skeletal muscle. J Biol Chem 1993; 268: 19019 - 19024.PubMedGoogle Scholar
  19. 19.
    Song WK, Wang W, Sato H et al. Expression of a7 integrin cytoplasmic domains during skeletal muscle development: alternate forms, conformational change, and homologies with serine/threonine kinases and tyrosine phosphatases. J Cell Sei 1993; 106: 1139 - 1152Google Scholar
  20. 20.
    Ziober BL, Vu MP, Waleh N et al. Alternative extracellular and cytoplasmic domains of the integrin a7 subunit are differentially expressed during development. J Biol Chem 1993; 268: 26773 - 26783.PubMedGoogle Scholar
  21. 21.
    Yang JT, Rayburn H, Hynes RO. Embryonic mesodermal defects in a5 integrin-deficient mice. Development 1993; 119: 1093 - 1105.PubMedGoogle Scholar
  22. 22.
    Yang JT, Rayburn H, Hynes RO. Cell adhesion events mediated by a4 integrins are essential in placental and cardiac development. Development 1995; 121: 549 - 60.PubMedGoogle Scholar
  23. 23.
    Gurtner GC, Davis V, Li H et al. Targeted disruption of the murine VCAM-1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation. Genes Dev 1995; 9: 1 - 14.CrossRefPubMedGoogle Scholar
  24. 24.
    Kwee L, Baldwin HS, Shen HM et al. Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. Development 1995; 121: 489 - 503.PubMedGoogle Scholar
  25. 25.
    Rosen GD, Sanes JR, LaChance R et al. Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis. Cell 1992; 69: 1107 - 1119.CrossRefPubMedGoogle Scholar
  26. 26.
    Huang XZ, Wu JF, Cass D et al. Inactivation of the integrin 136 subunit gene reveals a role of epithelial integrin in regulating inflammation in the lungs and skin. J Cell Biol 1996; 133: 1 - 8.CrossRefGoogle Scholar
  27. 27.
    George EL, Georges-Labouesse EN, Patel-King RS et al. Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 1993; 119: 1079 - 1091.PubMedGoogle Scholar
  28. 28.
    Ilic D, Furuta Y, Kanazawa S et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from mice. Nature 1995; 377: 539 - 543.CrossRefPubMedGoogle Scholar
  29. 29.
    Furuta Y, Ilic D, Kanazawa S et al. Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK. Oncogene 1995; 11: 1989 - 1995.PubMedGoogle Scholar
  30. 30.
    Vidal F, Aberdam D, Niguel C et al. Integrin 134 mutations associated with junctional epidermolysis bullosa with pyloric atresia. Nature Genet 1995; 10: 229 - 234.CrossRefPubMedGoogle Scholar
  31. 31.
    Gardner H, Kreidberg J, Koetliansky V et al. Deletion of integrin al by homologous recombination permits normal murine development but gives rise to a specific deficit in cell adhesion. Dev Biol 1996; 175: 301 - 313.CrossRefPubMedGoogle Scholar
  32. 32.
    Kadoya Y, Kadoya K, Durbeej M et al. Antibodies against E3 of laminin-1 and integrin a6 subunit perturb baranching epithelial morphogenesis of the embryonic submandibular gland, but by different modes. J Cell Biol 1995; 129: 521 - 534.CrossRefPubMedGoogle Scholar
  33. 33.
    Sorokin L, Sonnenberg A, Aumailley M et al. Recognition of the laminin E8 cell-binding site by an integrin possessing the a6 subunit is essential for epithelial polarization in developing kidney tubules. J Cell Biol 1990; 111, 1265 - 73.CrossRefPubMedGoogle Scholar
  34. 34.
    Wada J, Kumar A, Liu Z et al. Cloning of the mouse integrin av cDNA and role of av-related matrix receptors in metanephric development. J Cell Biol 1996; 132: 1161 - 1176.CrossRefPubMedGoogle Scholar
  35. 35.
    Martin PT, Kaufman SJ, Kramer RH et al. Synaptic integrins in developing, adult, and mutant muscle: selective association of al, a7A and a7B integrins with the neuromuscular junction. Dev Biol 1996; 174: 125 - 139.CrossRefPubMedGoogle Scholar
  36. 36.
    Forsberg E, Hirsch E, Fröhlich L et al. Skin wounds and severed nerves heal normally in mice lacking tenascin-C. Proc Natl Acad Sci USA 1996; 93: 6594 - 6599.CrossRefPubMedGoogle Scholar
  37. 37.
    Rudnicki MA, Jaenisch R. The MyoD family of transcription factors and skeletal myogenesis. Bioessays 1995; 17: 203 - 209.CrossRefPubMedGoogle Scholar
  38. 38.
    Patapoutian A, Yoon JK, Miner JH et al. Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the myotome. Development 1995; 121: 3347 - 3358.PubMedGoogle Scholar
  39. 39.
    Dalton SL, Scharf E, Briesewitz R et al. Cell adhesion to extracellular matrix regulates the life cycle of integrins. Mol Biol Cell 1995; 6: 1781 - 1791.PubMedGoogle Scholar
  40. 40.
    Campbell KP. Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell 1995; 80: 675 - 679.CrossRefPubMedGoogle Scholar
  41. 41.
    Lefaucheur JP, Pastoret C, Sebille A. Phenotype of dystrophinopathy in old mdx mice. Anat Rec 1995; 242: 70 - 76.CrossRefPubMedGoogle Scholar
  42. 42.
    Secof RL, Gerson I, Donady JJ et al. Drosophila myogenesis in vitro: the genesis of “small” myocytes and myotubes. Dev Biol 1973; 35: 250 - 261.CrossRefGoogle Scholar
  43. 43.
    Bate M. The embryonic development of larval muscles in Drosophila. Development 1990; 110: 791 - 804.PubMedGoogle Scholar
  44. 44.
    Michelson AM, Abmayr SM, Bate M et al. Expression of a MyoD family member prefigures muscle pattern in Drosophila embryos. Genes Dev 1990; 4: 2086 - 2097.CrossRefPubMedGoogle Scholar
  45. 45.
    Paterson BM, Walldorf U, Eldridge J et al. The Drosophila homologue of vertebrate myogenic-determination genes encodes a transiently expressed nuclear protein marking primary myogenic cells. Proc Natl Acad Sci USA 1991; 88: 3782 - 3786.CrossRefPubMedGoogle Scholar
  46. 46.
    Brower DL, Wilcox M, Piovant M et al. Related cell-surface antigens expressed with positional specificity in Drosophila imaginal discs. Proc Natl Acad Sci USA 1984; 81: 7485 - 7489.CrossRefPubMedGoogle Scholar
  47. 47.
    Wilcox M, Brower DL, Smith RJ. A position-specific cell surface antigen in the Drosophila wing imaginal disc. Cell 1981; 25: 159 - 164.CrossRefPubMedGoogle Scholar
  48. 48.
    Yee GH, Hynes RO. A novel, tissue specific integrin subunit, 13,i, expressed in the midgut of Drosophila melanogaster. Development 1993; 118: 845 - 858.PubMedGoogle Scholar
  49. 49.
    Gotwals PJ, Paine-Saunders SE, Stark KA et al. Drosophila integrins and their ligands. Curr Opin Cell Biol 1994; 6: 734 - 739.CrossRefPubMedGoogle Scholar
  50. 50.
    Gotwals P, Fessier LI, Wehrli M et al. Drosophila PSI integrin is a laminin receptor and differs in ligand specificity from PS2. Proc Natl Acad Sci USA 1994; 91: 11447 - 11451CrossRefPubMedGoogle Scholar
  51. 51.
    Fogerty FJ, Fessler LI, Bunch TA et al. Tiggrin, a novel Drosophila extracellular matrix protein that functions as a ligand for Drosophila aPS2RPSi integrins. Development 1994; 120: 1747 - 1758.PubMedGoogle Scholar
  52. 52.
    Brown NH, King DL, Wilcox M et al. Developmentally regulated alternative splicing of Drosophila integrin PS2 a transcripts. Cell 1989; 59: 185 - 195.CrossRefPubMedGoogle Scholar
  53. 53.
    Brown NH. Null mutations in the aPS2 and lips integrin subunit genes have distinct phenotypes. Development 1994; 120: 1221 - 1231.PubMedGoogle Scholar
  54. 54.
    Brower DL, Bunch TA, Mukai L et al. Nonequivalent requirements for PS1 and PS2 integrin at cell attachments in Drosophila:genetic analysis of the ap51 integrin subunit. Development 1995; 121: 1311 - 1320.PubMedGoogle Scholar
  55. 55.
    MacKrell AJ, Blumberg B, Haynes SR et al. The lethal myospheroid gene of Drosophila encodes a membrane protein homologous to vertebrate integrin 13 subunits. Proc Natl Acad Sci USA 1988; 85: 2633 - 2637.CrossRefPubMedGoogle Scholar
  56. 56.
    Volk T, Fessler LI, Fessler JH. A role for integrin in the formation of sarcomeric cytoarchitecture. Cell 1991; 63: 525 - 536.CrossRefGoogle Scholar
  57. 57.
    Brabant MC, Brower DL. PS2 integrin requirements in Drosophila embryo and wing morphogenesis. Dev Biol 1993; 157: 49 - 59.CrossRefPubMedGoogle Scholar
  58. 58.
    Wright TF. The phenogenetics of the embryonic mutant, lethal myospheroid, in Drosophila melanogaster. J Exp Zool 1960; 143: 77 - 99.CrossRefPubMedGoogle Scholar
  59. 59.
    Jaffredo T, Horwitz AF, Buck CA et al. Myoblast migration specifically inhibited in the chick embryo by grafted CSAT hybridoma cells secreting an anti-integrin antibody. Development 1988; 103: 131 - 446.Google Scholar
  60. 60.
    Menko S, Boettiger D. Occupation of the extracellular matrix receptor, integrin, is a control point for myogenic differentiation. Cell 1987; 51: 51 - 57.CrossRefPubMedGoogle Scholar
  61. 61.
    Worton R. Muscular dystrophies: diseases of the dystrophin-glycoprotein complex. Science 1995; 270: 755 - 756.CrossRefPubMedGoogle Scholar
  62. 62.
    Hughes SM, Blau HM. Migration of myoblasts across basal lamina during skeletal muscle development. Nature 1990; 345: 350 - 353.CrossRefPubMedGoogle Scholar
  63. 63.
    Bozyczko D, Decker C, Muschler J et al. Integrin on developing and adult skeletal muscle. Exp Cell Res 1989; 183: 72 - 91.CrossRefPubMedGoogle Scholar
  64. 64.
    Terracio L, Gullberg D, Rubin K et al. Expression of collagen adhesion adhesion protein and their association with the cytoskeleton in cardiac myocytes. Anat Rec 1989; 223: 62 - 71.CrossRefPubMedGoogle Scholar
  65. 65.
    McDonald KA, Lakonishok M, I lorwitz AF. av and a3 integrin subunits are associated with myofibrils during myofibrillogenesis. J Cell Sei 1995; 108: 975 - 983.Google Scholar
  66. 66.
    Bao ZZ, Lakonishok M, Kaufman S et al. a7131 integrin is a component of the myotendinous junction skeletal muscle. J Cell Sei 1993; 106: 579 - 590.Google Scholar
  67. 67.
    Bogaert T, Brown N, Wilcox M. The Drosophila PS2 antigen is an invertebrate integrin that, like the fibronectin receptor, becomes localized to muscle attachments. Cell 1987; 51: 929 - 940.CrossRefPubMedGoogle Scholar
  68. 68.
    Gullberg I), Veiling T, Sjiiberg G et al. Up-regulation of a novel integrin a-chain (amt) on human fetal myotubes. Dev Dyn 1995; 204: 57 - 65.Google Scholar
  69. 69.
    Veiling T, Collo G, Sorokin L et aI. Distinct a7A131 and a7B131 integrin expression patterns during mouse development. Dev Dyn 1996; 207: 355 - 371.CrossRefGoogle Scholar
  70. 70.
    Klein G, Ekblom M, Fecker L et al. Differential expression of laminin A and B chains during development of embryonic mouse organs. Development 1990; 110: 823 - 837.PubMedGoogle Scholar
  71. 71.
    Schuler F, Sorokin L. Expression of laminin isoforms in mouse myogenic cells in vitro and in vivo. J Cell Sci 1995; 108: 3795 - 3805.PubMedGoogle Scholar
  72. 72.
    Bladt F, Rietmacher D, Isenmann S et al. Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature 1995; 376: 768 - 771.CrossRefPubMedGoogle Scholar
  73. 73.
    Bober E, Franz T, Arnold HH et al. Pax-3 is required for the development of limb muscles: a possible role for the migration of dermomyotomal muscle progenitor cells. Development 1994; 120: 603 - 612.PubMedGoogle Scholar
  74. 74.
    Buckingham M. Muscle differentiation. Which myogenic factors make muscle ? Curr Biol 1994; 4: 61 - 63.CrossRefPubMedGoogle Scholar
  75. 75.
    Echtermeyer F, Schober S, Pöschl H et al. Specific induction of cell motility on laminin by a7 integrin. J Biol Chem 1995; 271: 2071 - 2075.Google Scholar
  76. 76.
    Thorsteinsdottir S, Roelen BAJ, Freund E et al. Expression patterns of laminin receptor splice variants a6Ai1 and a6B131 suggest different roles in mouse development. Dev Dyn 1995; 204: 240 - 258.CrossRefPubMedGoogle Scholar
  77. 77.
    Sonnenberg A, Linders CJ, Daams JH et al. The a6131 (VLA-6) and a6ß4 protein complexes: tissue distribution and biochemical properties. J Cell Sci 1990; 96: 207 - 217.PubMedGoogle Scholar
  78. 78.
    Aumailley M, Gimond C, Rousselle P. Integrin-mediated cellular interactions with laminins. In: Ekblom P, Timpl R, eds. The Laminins. Vol. 2. Amsterdam: Harwood Academic Publishers, 1996: 127 - 158.Google Scholar
  79. 79.
    Korhonen M, Ylänne J, Laitinen L et al. The al-a6 subunits of integrins are characteristically expressed in distinct segments of developing and adult human nephron. J Cell Biol 1990; 111: 1245 - 1254.CrossRefPubMedGoogle Scholar
  80. 80.
    Georges-Labouesse E, Messaddeq N, Yehia G et al. Absence of the alpha-6 integrin leads to epidermolysis bullosa and neonatal death in mice. Nature Genet 1996; 13: 370 - 373.CrossRefPubMedGoogle Scholar
  81. 81.
    van der Neut R, Krimpenfort P, Calafat J et al. Epithelial detachment due to absence of hemidesmosomes in integrin ß4 null mice. Nature Genet 1996; 13: 366 - 369.CrossRefPubMedGoogle Scholar
  82. 82.
    Durbeej M, Larsson E, IbraghimovBeskrovnaya O et al. Non-muscle alphadystroglycan is involved in epithelial development. J Cell Biol 1995; 130: 79 - 91.CrossRefPubMedGoogle Scholar
  83. 83.
    Anderson DC, Springer TA. Leucocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Ann Rev Medicine 1987; 38: 175 - 194.CrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 1997

Authors and Affiliations

  • Donald Gullberg
  • Peter Ekblom

There are no affiliations available

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