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Animal Models of Vascular Development and Endothelial Cell Biology

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Abstract

There have been great advances in the past 15 years in our understanding of how blood vessels form and function. Many of these advances result from the availability of several animal models that allow for embryological, molecular, and genetic manipulations of the developing vasculature. Here I describe four vertebrate animal models used in studies of vascular development. The frog, zebrafish, avian, and mouse embryos are compared historically and currently. Recent advances using each model are highlighted. Finally, I describe the use of animal derivatives, the chick chorioallantoic membrane and mouse embryonic stem cells, for studies of blood vessel formation.

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References

  1. Gilbert S. Developmental Biology. Sunderland, MA: Sinauer Associates, Inc., 2003:838.

    Google Scholar 

  2. Ghabrial A, Luschnig S, Metzstein MM, Krasnow MA. Branching morphogenesis of the Drosophila tracheal system. Annu Rev Cell Dev Biol 2003;19:623–647.

    Article  PubMed  CAS  Google Scholar 

  3. Kamei M, Brian Saunders W, Bayless KJ, Dye L, Davis GE, Weinstein BM. Endothelial tubes assemble from intracellular vacuoles in vivo. Nature 2006;442:453–456.

    Article  PubMed  CAS  Google Scholar 

  4. Rovainen C. Labeling of developing vascular endothelium after injections of rhodamine-dextran into blastomeres of Xenopus laevis. J Exp Zool 1991;259:209–221.

    Article  PubMed  CAS  Google Scholar 

  5. Mills KR, Kruep D, Saha MS. Elucidating the origins of the vascular system: A fate map of the vascular endothelial and red blood cell lineages in Xenopus laevis. Dev Biol 1999;209:352–368.

    Article  PubMed  CAS  Google Scholar 

  6. Cleaver O, Tonissen KF, Saha MS, Krieg PA. Neovascularization of the Xenopus embryo. Dev Dyn 1997;210:66–77.

    Article  PubMed  CAS  Google Scholar 

  7. Cleaver O, Krieg PA. Molecular mechanisms of vascular development. In: Harvey RP, Rosenthal N, Eds. Heart Development. New York: Academic Press, 1999:221–252.

    Google Scholar 

  8. Levine AJ, Munoz-Sanjuan I, Bell E, North AJ, Brivanlou AH. Fluorescent labeling of endothelial cells allows in vivo, continuous characterization of the vascular development of Xenopus laevis. Dev Biol 2003;254:50–67.

    Article  PubMed  CAS  Google Scholar 

  9. Carruthers S, Stemple DL. Genetic and genomic prospects for Xenopus tropicalis research. Sem Cell Dev Biol 2006;17:146–153.

    Article  CAS  Google Scholar 

  10. Ny A, Koch M, Schneider M, Neven E, Tong RT, Maity S, Fischer C, Plaisance S, Lambrechts D, Heligon C, Terclavers S, Ciesiolka M, Kalin R, Man WY, Senn I, Wyns S, Lupu F, Brandli A, Vleminckx K, Collen D, Dewerchin M, Conway EM, Moons L, Jain RK, Carmeliet P. A genetic Xenopus laevis tadpole model to study lymphangiogenesis. Nat Med 2005;11:998–1004.

    PubMed  CAS  Google Scholar 

  11. Streisinger G, Walker C, Dower N, Knauber D, Singer F. Production of clones of homozygous diploid zebra fish (Brachydanio rerio). Nature 1981;291:293–296.

    Article  PubMed  CAS  Google Scholar 

  12. Mullins MC, Hammerschmidt M, Haffter P, Nusslein-Volhard C. Large-scale mutagenesis in the zebrafish: In search of genes controlling development in a vertebrate. Curr Biol 1994;4:189–202.

    Article  PubMed  CAS  Google Scholar 

  13. Amsterdam A, Burgess S, Golling G, Chen W, Sun Z, Townsend K, Farrington S, Haldi M, Hopkins N. A large-scale insertional mutagenesis screen in zebrafish. Genes Dev 1999;13:2713–2724.

    Article  PubMed  CAS  Google Scholar 

  14. Isogai S, Horiguchi M, Weinstein BM. The vascular anatomy of the developing zebrafish: An atlas of embryonic and early larval development. Dev Biol 2001;230:278–301.

    Article  PubMed  CAS  Google Scholar 

  15. Lawson ND, Weinstein BM. In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol 2002;248:307–318.

    Article  PubMed  CAS  Google Scholar 

  16. Jin S-W, Beis D, Mitchell T, Chen J-N, Stainier DYR. Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development 2005;132:5199–5209.

    Article  PubMed  CAS  Google Scholar 

  17. Isogai S, Lawson ND, Torrealday S, Horiguchi M, Weinstein BM. Angiogenic network formation in the developing vertebrate trunk. Development 2003;130:5281–5290.

    Article  PubMed  CAS  Google Scholar 

  18. Weinstein BM. Vascular cell biology in vivo: A new piscine paradigm? Trends Cell Biol 2002;12:439–445.

    Article  PubMed  CAS  Google Scholar 

  19. Vogeli KM, Jin S-W, Martin GR, Stainier DYR. A common progenitor for haematopoietic and endothelial lineages in the zebrafish gastrula. Nature 2006;443:337–339.

    Article  PubMed  CAS  Google Scholar 

  20. Stainier DYR, Fouquet B, Chen J, Warren K, Weinstein BM, Meiler S, Mohi M, Neuhauss S, Solnica-Krezel L, Schier A, Zwartkruis F, Stemple DL, Driever W, Fishman MC. Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo. Development 1996;123:285–292.

    PubMed  CAS  Google Scholar 

  21. Weinstein BM. Plumbing the mysteries of vascular development using the zebrafish. Semin Cell Dev Biol 2002;13:515–522.

    Article  PubMed  Google Scholar 

  22. Peterson RT, Shaw SY, Peterson TA, Milan DJ, Zhong TP, Schreiber SL, MacRae CA, Fishman MC. Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation. Nat Biotechnol 2004;22:595–599.

    Article  PubMed  CAS  Google Scholar 

  23. Mukouyama YS, Shin D, Britsch S, Taniguchi M, Anderson DJ. Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin. Cell 2002;109:693–705.

    Article  PubMed  CAS  Google Scholar 

  24. le Noble F, Moyon D, Pardanaud L, Yuan L, Djonov V, Matthijsen R, Breant C, Fleury V, Eichmann A. Flow regulates arterial-venous differentiation in the chick embryo yolk sac. Development 2004; 131:361–375.

    Article  PubMed  CAS  Google Scholar 

  25. Lawson ND, Scheer N, Pham VN, Kim CH, Chitnis AB, Campos-Ortega JA, Weinstein BM. Notch signaling is required for arterialvenous differentiation during embryonic vascular development. Development 2001;128:3675–3683.

    PubMed  CAS  Google Scholar 

  26. Lawson ND, Vogel AM, Weinstein BM. Sonic hedgehog and vascular endothelial growth factor act upstream of the notch pathway during arterial endothelial differentiation. Dev Cell 2002;3:127–136.

    Article  PubMed  CAS  Google Scholar 

  27. Lawson ND, Mugford JW, Diamond BA, Weinstein BM. Phospholipase C gamma-1 is required downstream of vascular endothelial growth factor during arterial development. Genes Dev 2003;17: 1346–1351.

    Article  PubMed  CAS  Google Scholar 

  28. Pardanaud L, Altmann C, Kitos P, Dieterlen-Lievre F, Buck CA. Vasculogenesis in the early quail blastodisc as studied with a monoclonal antibody recognizing endothelial cells. Development 1987;100: 339–349.

    PubMed  CAS  Google Scholar 

  29. Coffin JD, Poole TJ. Embryonic vascular development: Immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos. Development 1988;102:735–748.

    PubMed  CAS  Google Scholar 

  30. Noden DM. Embryonic origins and assembly of blood vessels. Am Rev RespirDis 1989;140:1097–1103.

    CAS  Google Scholar 

  31. Pardanaud L, Yassine F, Dieterlen-Lievre F. Relationship between vasculogenesis, angiogenesis and haemopoiesis during avian ontogeny. Development 1989;105:473–485.

    PubMed  CAS  Google Scholar 

  32. Pardanaud L, Luton D, Prigent M, Bourcheix LM, Catala M, Dieterlen-Lievre F. Two distinct endothelial lineages in ontogeny, one of them related to hemopoiesis. Development 1996;122: 1363–1371.

    PubMed  CAS  Google Scholar 

  33. Iba H. Gene transfer into chicken embryos by retrovirus vectors. Dev Growth Differ 2000;42:213–218.

    Article  PubMed  CAS  Google Scholar 

  34. Ishii Y, Reese D, Mikawa T. Somatic transgenesis using retroviral vectors in the chicken embryo. Dev Dyn 2004;229:630–642.

    Article  PubMed  CAS  Google Scholar 

  35. Ogura T. In vivo electroporation: A new frontier for gene delivery and embryology. Differentiation 2002;70:163–171.

    Article  PubMed  CAS  Google Scholar 

  36. Swartz M, Eberhart J, Mastick GS, Krull CE. Sparking new frontiers: Using in vivo electroporation for genetic manipulations. Dev Biol 2001;233:13–21.

    Article  PubMed  CAS  Google Scholar 

  37. Bomberg-White J, Webb C, Patacsil V, Miranti C, Williams B, Holmen S. Delivery of short hairpin RNA sequences by using a replication-competent avian retroviral vector. J Virol 2004;78: 4914–4916.

    Article  CAS  Google Scholar 

  38. Rupp PA, Czirok A, Little CD. Novel approaches for the study of vascular assembly and morphogenesis in avian embryos. Trends Cardiovasc Med 2003;13:283–288.

    Article  PubMed  Google Scholar 

  39. Rupp PA, Czirok A, Little CD. αvβ3 integrin-dependent endothelial cell dynamics in vivo. Development 2004;131:2887–2897.

    Article  PubMed  CAS  Google Scholar 

  40. Ambler CA, Nowicki JL, Burke AC, Bautch VL. Assembly of trunk and limb blood vessels involves extensive migration and vasculogenesis of somite-derived angioblasts. Dev Biol 2001;234:352–364.

    Article  PubMed  CAS  Google Scholar 

  41. Ambler CA, Schmunk GA, Bautch VL. Stem cell-derived endothelial cells/progenitors migrate and pattern in the embryo using the VEGF signaling pathway. Dev Biol 2003;257:205–219.

    Article  PubMed  CAS  Google Scholar 

  42. Hogan KA, Ambler CA, Chapman DL, Bautch VL. The neural tube patterns vessels developmentally using the VEGF signaling pathway. Development 2004;131:1503–1513.

    Article  PubMed  CAS  Google Scholar 

  43. Norrby K. In vivo models of angiogenesis. J Cell Mol Med 2006;10:588–612.

    Article  PubMed  CAS  Google Scholar 

  44. Baldwin H, Shen H, Yan H, DeLisser H, Chung A, Mickanin C, Trask T, Kirschbaum N, Newman P, Albelda S. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): Alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development. Development 1994;120:2539–2553.

    PubMed  CAS  Google Scholar 

  45. DeLisser H, Christofidou-Solomidou M, Strieter R, Burdick M, Robinsion C, Wexler R, Kerr J, Garlanda C, Merwin J, Madri J, Albelda S. Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol 1997;151:671–677.

    PubMed  CAS  Google Scholar 

  46. Redick SD, Bautch VL. Developmental platelet endothelial cell adhesion molecule expression suggests multiple roles for a vascular adhesion molecule. Am J Pathol 1999;154:1137–1147.

    PubMed  CAS  Google Scholar 

  47. Nourshargh S, Krombach F, Dejana E. The role of JAM-A and PECAM-1 in modulating leukocyte infiltration in inflamed and ischemic tissues. J Leukoc Biol 2006;80:714–718.

    Article  PubMed  CAS  Google Scholar 

  48. Downing GJ, Battey JF Jr. Technical assessment of the first 20 years of research using mouse embryonic stem cell lines. Stem Cells 2004;22:1168–1180.

    Article  PubMed  Google Scholar 

  49. Shalaby F, Ho J, Stanford WL, Fischer KD, Schuh AC, Schwartz L, Bernstein A, Rossant J. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 1997;89:981–990.

    Article  PubMed  CAS  Google Scholar 

  50. Fong GH, Rossant J, Gertsenstein M, Breitman M. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995;376:66–70.

    Article  PubMed  CAS  Google Scholar 

  51. Metzger D, Chambon P. Site-and time-specific gene targeting in the mouse. Methods 2001;24:71–80.

    Article  PubMed  CAS  Google Scholar 

  52. Sauer B. Inducible gene targeting in mice using the cre/lox system. Methods 1998;6:381–392.

    Google Scholar 

  53. Gustafsson E, Brakebusch C, Hietanen K, Fassler R. Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice. J Cell Sci 2001;114:671–676.

    PubMed  CAS  Google Scholar 

  54. Kisanuki YY, Hammer RE, Miyazaki J-i, Williams SC, Richardson JA, Yanagisawa M. Tie2-Cre transgenic mice: A new model for endothelial cell-lineage analysis in vivo. Dev Biol 2001;230: 230–242.

    Article  PubMed  CAS  Google Scholar 

  55. Motoike T, Markham D, Rossant J, Sato T. Evidence for novel fate of Flk1 progenitor: Contribution to muscle lineage. Genesis 2003;35:153–159.

    Article  PubMed  Google Scholar 

  56. Alva JA, Zovein A, Monvoisin A, Murphy T, Salazar A, Harvey N, Carmeliet P, Iruela-Arispe M. VE-Cadherin-Cre-recombinase transgenic mouse: A tool for lineage analysis and gene deletion in endothelial cells. Dev Dyn 2006;235:759–767.

    Article  PubMed  CAS  Google Scholar 

  57. Forde A, Constien R, Grone H, Hammerling G, Arnold B. Temporal Cre-mediated recombination exclusively in endothelial cells using Tie2 regulatory elements. Genesis 2002;33:191–197.

    Article  PubMed  CAS  Google Scholar 

  58. Gothert JR, Gustin SE, Hall MA, Green AR, Gottgens B, Izon DJ, Begley CG. In vivo fate-tracing studies using the Scl stem cell enhancer: Embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis. Blood 2005;105:2724–2732.

    Article  PubMed  CAS  Google Scholar 

  59. Eichmann A, Yuan L, Moyon D, le Noble F, Pardanaud L, Breant C. Vascular development: From precursor cells to branched arterial and venous networks. Int J Dev Biol 2005;49:259–267.

    Article  PubMed  CAS  Google Scholar 

  60. Gitler AD, Lu MM, Epstein JA. PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development. Dev Cell 2004;7:107–116.

    Article  PubMed  CAS  Google Scholar 

  61. Lu X, le Noble F, Yuan L, Jiang Q, de Lafarge B, Sugiyama D, Breant C, Claes F, De Smet F, Thomas J-L, Autiero M, Carmeliet P, Tessier-Lavigne M, Eichmann A. The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 2004;432:179–186.

    Article  PubMed  CAS  Google Scholar 

  62. Park KW, Crouse D, Lee M, Karnik SK, Sorensen LK, Murphy KJ, Kuo CJ, Li DY. The axonal attractant Netrin-1 is an angiogenic factor. Proc Natl Acad Sci USA 2004;101:16210–16215.

    Article  PubMed  CAS  Google Scholar 

  63. Wilson BD, Ii M, Park KW, Suli A, Sorensen LK, Larrieu-Lahargue F, Urness LD, Suh W, Asai J, Kock GAH, Thorne T, Silver M, Thomas KR, Chien C-B, Losordo DW, Li DY. Netrins promote developmental and therapeutic angiogenesis. Science 2006;313: 640–644.

    Article  PubMed  CAS  Google Scholar 

  64. Barber CL, Iruela-Arispe ML. The ever-elusive endothelial progenitor cell: Identities, functions and clinical implications. Pediatr Res 2006;59:26R–32R.

    Article  PubMed  Google Scholar 

  65. Doetschman TC, Eistetter H, Katz M, Schmidt W, Kemler R. The in vitro development of blastocyst-derived embryonic stem cell lines: Formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol 1985;87:27–45.

    PubMed  CAS  Google Scholar 

  66. Risau W, Sariola H, Zerwes HG, Sasse J, Ekblom P, Kemler R, Doetschman T. Vasculogenesis and angiogenesis in embryonicstem-cell-derived embryoid bodies. Development 1988;102:471–478.

    PubMed  CAS  Google Scholar 

  67. Bautch VL. Embryonic stem cell differentiation and the vascular lineage. In: Turksen K, Ed. Methods in Molecular Biology, Vol. 185, Embryonic Stem Cells: Methods and Protocols. Totowa, NJ: Humana Press, 2001:117–125.

    Google Scholar 

  68. Kearney JB, Bautch VL. In vitro differentiation of mouse ES cells: Hematopoietic and vascular development. Methods Enzymol 2003;365:83–98.

    Article  PubMed  Google Scholar 

  69. Bautch VL, Stanford WL, Rapoport R, Russell S, Byrum RS, Futch TA. Blood island formation in attached cultures of murine embryonic stem cells. Dev Dyn 1996;205:1–12.

    Article  PubMed  CAS  Google Scholar 

  70. Bautch VL, Redick SD, Scalia A, Harmaty M, Carmeliet P, Rapoport R. Characterization of the vasculogenic block in the absence of vascular endothelial growth factor-A. Blood 2000;95:1979–1987.

    PubMed  CAS  Google Scholar 

  71. Ramirez-Bergeron DL, Runge A, Dahl KDC, Fehling HJ, Keller G, Simon MC. Hypoxia affects mesoderm and enhances hemangioblast specification during early development. Development 2004;131: 4623–4634.

    Article  PubMed  CAS  Google Scholar 

  72. Kearney JB, Kappas NC, Ellerstrom C, DiPaola FW, Bautch VL. The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood 2004;103: 4527–4535.

    Article  PubMed  CAS  Google Scholar 

  73. Choi K, Kennedy M, Kazarov A, Papadimitriou J, Keller G. A common precursor for hematopoietic and endothelial cells. Development 1998;125:725–732.

    PubMed  CAS  Google Scholar 

  74. Park C, Ma YD, Choi K. Evidence for the hemangioblast. Exp Hematol 2005;33:965–970.

    Article  PubMed  CAS  Google Scholar 

  75. Huber TL, Kouskoff V, Joerg Fehling H, Palis J, Keller G. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 2004;432:625–630.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC

    Victoria L. Bautch PhD

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  1. Victoria L. Bautch PhD
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Editors and Affiliations

  1. Oregon National Primate Research Center, Beaverton, OR

    P. Michael Conn PhD (Associate Director and Senior Scientist, Professor of Physiology and Pharmacology, Professor of Cell and Developmental Biology) (Associate Director and Senior Scientist, Professor of Physiology and Pharmacology, Professor of Cell and Developmental Biology)

  2. Oregon Health and Science University, Portland, OR

    P. Michael Conn PhD (Associate Director and Senior Scientist, Professor of Physiology and Pharmacology, Professor of Cell and Developmental Biology) (Associate Director and Senior Scientist, Professor of Physiology and Pharmacology, Professor of Cell and Developmental Biology)

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Bautch, V.L. (2008). Animal Models of Vascular Development and Endothelial Cell Biology. In: Conn, P.M. (eds) Sourcebook of Models for Biomedical Research. Humana Press. https://doi.org/10.1007/978-1-59745-285-4_38

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  • DOI: https://doi.org/10.1007/978-1-59745-285-4_38

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-933-8

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