Download PDF
Thromb Haemost 2000; 84(06): 1023-1030
DOI: 10.1055/s-0037-1614166
Review Article
Schattauer GmbH

Early Embryonic Expression of Murine Coagulation System Components

Kelly Ong
1   From the Institute of Medical Sciences, Toronto, Ontario, Canada
,
Wendy Horsfall
1   From the Institute of Medical Sciences, Toronto, Ontario, Canada
2   The Departments of Medicine, Toronto, Ontario, Canada
,
Edward M. Conway
1   From the Institute of Medical Sciences, Toronto, Ontario, Canada
2   The Departments of Medicine, Toronto, Ontario, Canada
3   Medical Biophysics, Toronto, Ontario, Canada
4   University of Toronto, and the Division of Hematology/Oncology, The Toronto Hospital, Toronto, Ontario, Canada
5   Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium
,
Andre C. Schuh
1   From the Institute of Medical Sciences, Toronto, Ontario, Canada
2   The Departments of Medicine, Toronto, Ontario, Canada
3   Medical Biophysics, Toronto, Ontario, Canada
4   University of Toronto, and the Division of Hematology/Oncology, The Toronto Hospital, Toronto, Ontario, Canada
› Author AffiliationsThe authors thank Xiang-Fu Wu for technical assistance, Daniel Dumont for helpful discussions, and Norman Lassam for reviewing the manuscript. This work was supported by grants from The Heart and Stroke Foundation of Ontario, Canada (EMC) and the Medical Research Council of Canada (ACS).
Further Information

Publication History

Received 17 December 1999

Accepted after resubmission 01 June 2000

Publication Date:
13 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

The development of the embryonic coagulation system, and its contribution to the maintenance of vascular integrity during the formation of embryonic blood vessels, remain poorly understood. We have characterized the temporal expression patterns of 27 hemostasis-related genes during murine development. We show that, although most coagulation and fibrinolysis-related factors are expressed coordinately b 7.5 dpc, several, including FIX, FXII and PAI2, are not detectable until later developmental timepoints. The expression of hemostasis-specific genes prior to the formation of a functional circulatory system supports the view that some coagulation factors have additional non-hemostatic functions during development. In addition, the discordant expression of some factors suggests that the embryonic hemostatic system may be distinct from that of the adult. These analyses will help to elucidate the regulation of hemostasis during embryonic/vascular development, and will provide a framework to facilitate the interpretation of gene inactivation studies.

Keywords

Embryo - hemostasis - vascular development - knock-out
 

  • References

  • 1 Broze Jr. G. Tissue factor pathway inhibitor and the current concept of blood coagulation. Blood Coag Fibrinolys 1995; 06: S7-S13.
    PubMedGoogle Scholar
  • 2 Hajjar KA. Changing concepts in fibrinolysis. Curr Opin Hematol 1995; 02: 345-50.
    CrossrefPubMedGoogle Scholar
  • 3 Nesheim M, Wang W, Boffa M, Nagashima M, Morser J, Bajzar L. Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thromb Haemost 1997; 78: 386-91.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Andrew M, Paes B. Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hematol Oncol 1990; 12: 95-104.
    CrossrefPubMedGoogle Scholar
  • 5 Andrew M. The relevance of developmental hemostasis to hemorrhagic disorders of newborns. Semin Perinatol 1997; 21: 70-85.
    CrossrefPubMedGoogle Scholar
  • 6 Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen D, Powers P. Development of the human coagulation system in the full-term infant. Blood 1987; 70: 165-72.
    PubMedGoogle Scholar
  • 7 Ries M. Molecular and functional properties of fetal plasminogen and its possible influence on clot lysis in the neonatal period. Semin Thromb Hemost 1997; 23: 247-52.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Bussolino F, Mantovani A, Persico G. Molecular mechanisms of blood vessel formation. Trends Biochem Sci 1997; 22: 251-6.
    CrossrefPubMedGoogle Scholar
  • 9 Noden D. Embryonic origins and assembly of blood vessels. Am Rev Resp Dis 1989; 140: 1097-103.
    PubMedGoogle Scholar
  • 10 Noden D. Development of craniofacial blood vessels. In: The development of the vascular system. Feinberg R, Sherer G, Auerbach R. New York: 1991: 1-24.
    Google Scholar
  • 11 Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671-4.
    CrossrefPubMedGoogle Scholar
  • 12 Risau W. Differentiation of endothelium. Faseb J 1995; 09: 926-33.
    CrossrefPubMedGoogle Scholar
  • 13 Risau W. Vasculogenesis, angiogenesis and endothelial cell differentiation during embryo development. In: The development of the vascular system. Feinberg R, Sherer G, Auerbach R. New York: Karger; 1991: 58-68.
    Google Scholar
  • 14 Risau W. Development and differentiation of endothelium. Kidney Int Suppl 1998; 67: S3-6.
    PubMedGoogle Scholar
  • 15 Soifer SJ, Peters KG, O’Keefe J, Coughlin SR. Disparate temporal expression of the prothrombin and thrombin receptor genes during mouse development. Am J Pathol 1994; 144: 60-9.
    PubMedGoogle Scholar
  • 16 Darrow AL, Fung-Leung WP, Ye RD, Santulli RJ, Cheung WM, Derian CK, Burns CL, Damiano BP, Zhou L, Keenan CM, Peterson PA, Andrade-Gordon P. Biological consequences of thrombin receptor deficiency in mice. Thromb Haemost 1996; 76: 860-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Cui J, O’Shea KS, Purkayastha A, Saunders TL, Ginsburg D. Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Nature 1996; 384: 66-8.
    CrossrefPubMedGoogle Scholar
  • 18 Connolly A, Ishihara H, Kahn M, Farese Jr R, Coughlin S. Role of the thrombin receptor in development and evidence for a second receptor. Nature 1996; 381: 516-9.
    CrossrefPubMedGoogle Scholar
  • 19 Healy A, Rayburn H, Rosenberg R, Weiler H. Absence of the blood-clotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system. Proc Natl Acad Sci (USA) 1995; 92: 850-4.
    CrossrefPubMedGoogle Scholar
  • 20 Carmeliet P, Mackman N, Moons L, Luther T, Gressens P, Van Vlaenderen I, Demunck H, Kasper M, Breier G, Evrard P, Muller M, Risau W, Edgington T, Collen D. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383: 73-5.
    CrossrefPubMedGoogle Scholar
  • 21 Bugge T, Xiao Q, Kombrinck K, Flick M, Holmback K, Danton M, Colbert M, Witte D, Fujikawa K, Davie E, Degen J. Fatal embryonic bleeding events in mice lacking tissue factor, the cell associated initiator of blood coagulation. Proc Natl Acad Sci (USA) 1996; 93: 6258-63.
    CrossrefPubMedGoogle Scholar
  • 22 Toomey JR, Kratzer KE, Lasky NM, Stanton JJ, Broze Jr GJ. Targeted disruption of the murine tissue factor gene results in embryonic lethality. Blood 1996; 88: 1583-7.
    PubMedGoogle Scholar
  • 23 Wiles MV. Embryonic stem cell differentiation in vitro. Methods Enzymol 1993; 225: 900-18.
    PubMedGoogle Scholar
  • 24 Keller G, Kennedy M, Papayannopoulou T, Wiles M. Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol 1993; 13: 473-86.
    CrossrefPubMedGoogle Scholar
  • 25 Weiss M, Keller G, Orkin S. Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. Genes & Dev 1994; 08: 1184-97.
    PubMedGoogle Scholar
  • 26 Vittet D, Prandini M, Berthier R, Schweitzer A, Martin-Sisteron H, Uzqn G, Dejana E. Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps. Development 1996; 88: 3424-31.
    PubMedGoogle Scholar
  • 27 Dumont DJ, Fong GH, Puri MC, Gradwohl G, Alitalo K, Breitman ML. Vascularization of the mouse embryo: a study of flk-1, tek, tie, and vascular endothelial growth factor expression during development. Dev Dyn 1995; 203: 80-92.
    CrossrefPubMedGoogle Scholar
  • 28 Wang M, Clark R, Bautch V. Embryonic stem-cell derived cystic embyroid bodies from vascular channels: an in vitro model of blood vessel development. Development 1992; 114: 303-16.
    PubMedGoogle Scholar
  • 29 Risau W, Sariola H, Zerwes HG, Sasse J, Ekblom P, Kemler R, Doetschman T. Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 1988; 102: 471-8.
    PubMedGoogle Scholar
  • 30 Luther T, Flossel C, Mackman N, Bierhaus A, Kasper M, Albrecht S, Sage EH, Iruela-Arispe L, Grossmann H, Strohlein A, Zhang Y, Nawroth PP, Carmeliet P, Loskutoff DJ, Muller M. Tissue factor expression during human and mouse development. Am J Pathol 1996; 149: 101-13.
    PubMedGoogle Scholar
  • 31 Sun WY, Witte DP, Degen JL, Colbert MC, Burkart MC, Holmback K, Xiao Q, Bugge TH, Degen SJ. Prothrombin deficiency results in embryonic and neonatal lethality in mice. Proc Natl Acad Sci (USA) 1998; 95: 7597-602.
    CrossrefPubMedGoogle Scholar
  • 32 Imada S, Yamaguchi H, Nagumo M, Katayanagi S, Iwasaki H, Imada M. Identification of fetomodulin, a surface marker protein of fetal development, as thrombomodulin by gene cloning and functional assays. Dev Biol 1990; 140: 113-22.
    CrossrefPubMedGoogle Scholar
  • 33 Tsakiris DA, Scudder L, Hodivala-Dilke K, Hynes RO, Coller BS. Hemostasis in the mouse (Mus musculus): a review. Thromb Haemost 1999; 81: 177-88.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Xue J, Wu Q, Westfield LA, Tuley EA, Lu D, Zhang Q, Shim K, Zheng X, Sadler JE. Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice. Proc Natl Acad Sci (USA) 1998; 95: 7603-7.
    CrossrefPubMedGoogle Scholar
  • 35 Huang ZF, Broze Jr G. Consequences of tissue factor pathway inhibitor gene- disruption in mice. Thromb Haemost 1997; 78: 699-704.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Mueller B, Reisfeld R, Edgington T, Ruf W. Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci (USA) 1992; 89: 11832-6.
    CrossrefPubMedGoogle Scholar
  • 37 Ott I, Fischer EG, Miyagi Y, Mueller BM, Ruf W. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998; 140: 1241-53.
    CrossrefPubMedGoogle Scholar
  • 38 Fischer EG, Riewald M, Huang H-Y, Miyagi H, Kubota Y, Mueller BM, Ruf W. Tumor cell adhesion and migration supported by interaction of a receptor-protease complex with its inhibitor. J Clin Invest 1999; 104: 1213-21.
    CrossrefPubMedGoogle Scholar
  • 39 Gasic G, Arenas C, Gasic T, Basic G. Coagulation factors X, Xa and protein S as potent mitogens of cultured aortic smooth muscle cells. Proc Natl Acad Sci (USA) 1992; 89: 2317-20.
    CrossrefPubMedGoogle Scholar
  • 40 Zhang Y, Weiler-Guettler H, Chen J, Wilhelm O, Deng Y, Qiu F, Nakagawa K, Klevesath M, Wilhelm S, Bohrer H, Nakagawa M, Graeff H, Martin E, Stern D, Rosenberg R, Ziegler R, Nawroth P. Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity. J Clin Invest 1998; 101: 1301-9.
    CrossrefPubMedGoogle Scholar
  • 41 Romer J, Bugge T, Pyke C, Lund L, Flick M, Degen J, Dano K. Impaired wound healing in mice with a disrupted plasminogen gene. Nature Medicine 1996; 02: 287-92.
    CrossrefPubMedGoogle Scholar
  • 42 Carmeliet P, Bouche A, De Clercq C, Janssen S, Pollefeyt S, Wyns S, Mulligan R, Collen D. Biological effects of disruption of tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor-1 genes in mice. Ann N Y Acad Sci 1995; 748: 367-81.
    PubMedGoogle Scholar
  • 43 Stitt TN, Conn G, Gore M, Lai C, Bruno J, Radziejewski C, Mattsson K, Fisher J, Gies DR, Jones PF. et al. The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell 1995; 80: 661-70.
    CrossrefPubMedGoogle Scholar
  • 44 O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315-28.
    CrossrefPubMedGoogle Scholar
  • 45 Cirino G, Cicala C, Bucci M, Sorrentino L, Ambrosini G, DeDominicis G, Altieri D. Factor Xa as an interface between coagulation and inflammation. J Clin Invest 1997; 99: 2446-51.
    CrossrefPubMedGoogle Scholar
  • 46 Esmon C, Taylor F, Snow T. Inflammation and coagulation: linked processes potentially mediated by protein C. Thromb Haemost 1991; 66: 160-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Monsonego A, Mizrahi T, Eitan S, Moalem G, Bardos H, Adany R, Schwartz M. Factor XIIIa as a nerve-associated transglutaminase. Faseb J 1998; 12: 1163-71.
    CrossrefPubMedGoogle Scholar
  • 48 Schmaier AH. Contact activation: a revision. Thromb Haemost 1997; 78: 101-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Tkachuk V, Stepanova V, Little PJ, Bobik A. Regulation and role of urokinase plasminogen activator in vascular remodelling. Clin Exp Pharmacol Physiol 1996; 23: 759-65.
    CrossrefPubMedGoogle Scholar
  • 50 Kundu RK, Sangiorgi F, Wu LY, Kurachi K, Anderson WF, Maxson R, Gordon EM. Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice. Blood 1998; 92: 168-74.
    PubMedGoogle Scholar
  • 51 Bi L, Lawler A, Antonarakis S, High K, Gerhart J, Kazazian H. Targeted disruption of the mouse factor VIII gene produces a model of hemophilia A. Nat Genet 1995; 69: 21-4.
    PubMedGoogle Scholar
  • 52 Ranganathan G, Blatti SP, Subramaniam M, Fass DN, Maihle NJ, Getz MJ. Cloning of murine tissue factor and regulation of gene expression by transforming growth factor type beta 1. J Biol Chem 1991; 266: 496-501.
    PubMedGoogle Scholar
  • 53 Murakawa M, Okamura T, Kamura T, Shibuya T, Harada M, Niho Y. Diversity of primary structures of the carboxy-terminal regions of mammalian fibrinogen A alpha-chains. Characterization of the partial nucleotide and deduced amino acid sequences in five mammalian species; rhesus monkey, pig, dog, mouse and Syrian hamster. Thromb Haemost 1993; 69: 351-60.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Degen SJ, Schaefer LA, Jamison CS, Grant SG, Fitzgibbon JJ, Pai JA, Chapman VM, Elliott RW. Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2. DNA Cell Biol 1990; 09: 487-98.
    CrossrefPubMedGoogle Scholar
  • 55 Bugge TH, Suh TT, Flick MJ, Daugherty CC, Romer J, Solberg H, Ellis V, Dano K, Degen JL. The receptor for urokinase-type plasminogen activator is not essential for mouse development or fertility. J Biol Chem 1995; 270: 16886-94.
    CrossrefPubMedGoogle Scholar
  • 56 Idusogie E, Rosen E, Geng JP, Carmeliet P, Collen D, Castellino FJ. Characterization of a cDNA encoding murine coagulation factor VII. Thromb Haemost 1996; 75: 481-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 57 Elder B, Lakich D, Gitschier J. Sequence of the murine factor VIII cDNA. Genomics 1993; 16: 374-9.
    CrossrefPubMedGoogle Scholar
  • 58 Nichols WC, Cooney KA, Mohlke KL, Ballew JD, Yang A, Bruck ME, Reddington M, Novak EK, Swank RT, Ginsburg D. von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene. Blood 1994; 83: 3225-31.
    PubMedGoogle Scholar
  • 59 Sarkar G, Koeberl DD, Sommer SS. Direct sequencing of the activation peptide and the catalytic domain of the factor IX gene in six species. Genomics 1990; 06: 133-43.
    CrossrefPubMedGoogle Scholar
  • 60 Rosen E. Personal Communication. 1997
    PubMed
  • 61 Genbank Accession number X99571.
    PubMed
  • 62 Nonaka M, Matsuda Y, Shiroishi T, Moriwaki K, Natsuume-Sakai S. Molecular cloning of the b subunit of mouse coagulation factor XIII and assignment of the gene to chromosome 1: close evolutionary relationship to complement factor H. Genomics 1993; 15: 535-42.
    CrossrefPubMedGoogle Scholar
  • 63 Wu JK, Sheffield WP, Blajchman MA. Molecular cloning and cell-free expression of mouse antithrombin III. Thromb Haemost 1992; 68: 291-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 64 Tada N, Sato M, Tsujimura A, Iwase R, Hashimoto-Gotoh T. Isolation and characterization of a mouse protein C cDNA. J Biochem (Tokyo) 1992; 111: 491-5.
    CrossrefPubMedGoogle Scholar
  • 65 Fukudome K, Esmon CT. Molecular cloning and expression of murine and bovine endothelial cell protein C/activated protein C receptor (EPCR). The structural and functional conservation in human, bovine, and murine EPCR. J Biol Chem 1995; 270: 5571-5.
    CrossrefPubMedGoogle Scholar
  • 66 Chu MD, Sun J, Bird P. Cloning and sequencing of a cDNA encoding the murine vitamin K-dependent protein S. Biochim Biophys Acta 1994; 1217: 325-8.
    CrossrefPubMedGoogle Scholar
  • 67 Dittman WA, Majerus PW. Sequence of a cDNA for mouse thrombomodulin and comparison of the predicted mouse and human amino acid sequences. Nucleic Acids Res 1989; 17: 802.
    CrossrefPubMedGoogle Scholar
  • 68 Genbank. Accession number L03529.
    PubMed
  • 69 Genbank. Accession number U92972.
    PubMed
  • 70 Ong K, Conway EM, Schuh AC. Unpublished data. 1997
    PubMedGoogle Scholar
  • 71 Degen SJ, Bell SM, Schaefer LA, Elliott RW. Characterization of the cDNA coding for mouse plasminogen and localization of the gene to mouse chromosome 17. Genomics 1990; 08: 49-61.
    CrossrefPubMedGoogle Scholar
  • 72 Rickles RJ, Darrow AL, Strickland S. Molecular cloning of complementary DNA to mouse tissue plasminogen activator mRNA and its expression during F9 teratocarcinoma cell differentiation. J Biol Chem 1988; 263: 1563-9.
    PubMedGoogle Scholar
  • 73 Belin D, Vassalli JD, Combepine C, Godeau F, Nagamine Y, Reich E, Kocher HP, Duvoisin RM. Cloning, nucleotide sequencing and expression of cDNAs encoding mouse urokinase-type plasminogen activator. Eur J Biochem 1985; 148: 225-32.
    CrossrefPubMedGoogle Scholar
  • 74 Kristensen P, Eriksen J, Blasi F, Dano K. Two alternatively spliced mouse urokinase receptor mRNAs with different histological localization in the gastrointestinal tract. J Cell Biol 1991; 115: 1763-71.
    CrossrefPubMedGoogle Scholar
  • 75 Prendergast GC, Diamond LE, Dahl D, Cole MD. The c-myc-regulated gene mrl encodes plasminogen activator inhibitor 1. Mol Cell Biol 1990; 10: 1265-9.
    CrossrefPubMedGoogle Scholar
  • 76 Liang Z, Cooper A, DeFord ME, Carmeliet P, Collen D, Castellino FJ. Rosen Cloning and characterization of a cDNA encoding murine coagulation factor X. Thromb Haemost 1998; 80: 87-91.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 77 Menoud PA, Sappino N, Boudal-Khoshbeen M, Vassalli JD, Sappino AP. The kidney is a major site of alpha(2)-antiplasmin production. J Clin Invest 1996; 97: 2478-84.
    CrossrefPubMedGoogle Scholar
  • 78 Conway EM, Schuh AC. Unpublished data, 1997.
    PubMed