Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. From the onset of blood flow, the embryonic vasculature is continuously exposed to a variety of hemodynamic forces. These biomechanical stimuli are key determinants of vascular cell specification and remodeling and the establishment of vascular homeostasis. In recent years, major advances have been made in our understanding of mechano-activated signaling networks that control both spatiotemporal and structural aspects of vascular development. It has become apparent that a major site for mechanotransduction is situated at the interface of blood and the vessel wall and that this process is controlled by the vascular endothelium. In this review, we discuss the hemodynamic control of endothelial cell fates, focusing on arterial-venous specification, lymphatic development, and the endothelial-to-hematopoietic transition, and present some recent insights into the mechano-activated pathways driving these cell fate decisions in the developing embryo.


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Literature Cited

  1. Adamo L, García-Cardeña G. 2012. The vascular origin of hematopoietic cells. Dev. Biol. 362:1–10 [Google Scholar]
  2. Adamo L, Naveiras O, Wenzel PL, McKinney-Freeman S, Mack PJ. et al. 2009. Biomechanical forces promote embryonic haematopoiesis. Nature 459:1131–35 [Google Scholar]
  3. Baeyens N, Bandyopadhyay C, Coon BG, Yun S, Schwartz MA. 2016. Endothelial fluid shear stress sensing in vascular health and disease. J. Clin. Investig. 126:821–28 [Google Scholar]
  4. Baeyens N, Nicoli S, Coon BG, Ross TD, Van den Dries K. et al. 2015. Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point. eLife 4:e04645 [Google Scholar]
  5. Banjo T, Grajcarek J, Yoshino D, Osada H, Miyasaka KY. et al. 2013. Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21. Nat. Commun. 4:1978 [Google Scholar]
  6. Barakat AI. 2001. A model for shear stress–induced deformation of a flow sensor on the surface of vascular endothelial cells. J. Theor. Biol. 210:221–36 [Google Scholar]
  7. Barakat AI, Leaver EV, Pappone PA, Davies PF. 1999. A flow-activated chloride-selective membrane current in vascular endothelial cells. Circ. Res. 85:820–28 [Google Scholar]
  8. Blackman BR, García-Cardeña G, Gimbrone MA Jr. 2002. A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. J. Biomech. Eng. 124:397–407 [Google Scholar]
  9. Boardman KC, Swartz MA. 2003. Interstitial flow as a guide for lymphangiogenesis. Circ. Res. 92:801–8 [Google Scholar]
  10. Boon RA, Leyen TA, Fontijn RD, Fledderus JO, Baggen JM. et al. 2010. KLF2-induced actin shear fibers control both alignment to flow and JNK signaling in vascular endothelium. Blood 115:2533–42 [Google Scholar]
  11. Boyd NL, Park H, Yi H, Boo YC, Sorescu GP. et al. 2003. Chronic shear induces caveolae formation and alters ERK and Akt responses in endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 285:H1113–22 [Google Scholar]
  12. Brooks AR, Lelkes PI, Rubanyi GM. 2002. Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol. Genom. 9:27–41 [Google Scholar]
  13. Chapman WB. 1918. The effect of the heart-beat upon the development of the vascular system in the chick. Am. J. Anat. 23:175–203 [Google Scholar]
  14. Chen BP, Li YS, Zhao Y, Chen KD, Li S. et al. 2001. DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress. Physiol. Genom. 7:55–63 [Google Scholar]
  15. Chen CY, Bertozzi C, Zou Z, Yuan L, Lee JS. et al. 2012. Blood flow reprograms lymphatic vessels to blood vessels. J. Clin. Investig. 122:2006–17 [Google Scholar]
  16. Chiu JJ, Chien S. 2011. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol. Rev. 91:327–87 [Google Scholar]
  17. Coon BG, Baeyens N, Han J, Budatha M, Ross TD. et al. 2015. Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex. J. Cell Biol. 208:975–86 [Google Scholar]
  18. Corti P, Young S, Chen CY, Patrick MJ, Rochon ER. et al. 2011. Interaction between alk1 and blood flow in the development of arteriovenous malformations. Development 138:1573–82 [Google Scholar]
  19. Coste B, Xiao B, Santos JS, Syeda R, Grandl J. et al. 2012. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483:176–81 [Google Scholar]
  20. Culver JC, Dickinson ME. 2010. The effects of hemodynamic force on embryonic development. Microcirculation 17:164–78 [Google Scholar]
  21. Davies PF. 1995. Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75:519–60 [Google Scholar]
  22. Davies PF, Barbee KA, Volin MV, Robotewskyj A, Chen J. et al. 1997. Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction. Annu. Rev. Physiol. 59:527–49 [Google Scholar]
  23. Davies PF, Dewey CF Jr., Bussolari SR, Gordon EJ, Gimbrone MA Jr. 1984. Influence of hemodynamic forces on vascular endothelial function. In vitro studies of shear stress and pinocytosis in bovine aortic cells. J. Clin. Investig. 73:1121–29 [Google Scholar]
  24. Dekker RJ, van Thienen JV, Rohlena J, de Jager SC, Elderkamp YW. et al. 2005. Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am. J. Pathol. 167:609–18 [Google Scholar]
  25. Dewey JF. 1981. Regional tectonics. Science 214:550–51 [Google Scholar]
  26. Diaz MF, Li N, Lee HJ, Adamo L, Evans SM. et al. 2015. Biomechanical forces promote blood development through prostaglandin E2 and the cAMP-PKA signaling axis. J. Exp. Med. 212:665–80 [Google Scholar]
  27. Dietrich AC, Lombardo VA, Veerkamp J, Priller F, Abdelilah-Seyfried S. 2014. Blood flow and Bmp signaling control endocardial chamber morphogenesis. Dev. Cell 30:367–77 [Google Scholar]
  28. Egorova AD, Van der Heiden K, Van de Pas S, Vennemann P, Poelma C. et al. 2011. Tgfβ/Alk5 signaling is required for shear stress induced klf2 expression in embryonic endothelial cells. Dev. Dyn. 240:1670–80 [Google Scholar]
  29. Eyckmans J, Boudou T, Yu X, Chen CS. 2011. A hitchhiker's guide to mechanobiology. Dev. Cell 21:35–47 [Google Scholar]
  30. Fisher AB, Al-Mehdi AB, Manevich Y. 2002. Shear stress and endothelial cell activation. Crit. Care Med. 30:S192–97 [Google Scholar]
  31. Florian JA, Kosky JR, Ainslie K, Pang Z, Dull RO, Tarbell JM. 2003. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circ. Res. 93:e136–42 [Google Scholar]
  32. Gaengel K, Niaudet C, Hagikura K, Lavina B, Muhl L. et al. 2012. The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev. Cell 23:587–99 [Google Scholar]
  33. García-Cardeña G, Comander J, Anderson KR, Blackman BR, Gimbrone MA Jr. 2001. Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. PNAS 98:4478–85 [Google Scholar]
  34. Garcia-Porrero JA, Godin IE, Dieterlen-Lièvre F. 1995. Potential intraembryonic hemogenic sites at pre-liver stages in the mouse. Anat. Embryol. 192:425–35 [Google Scholar]
  35. Garcia-Porrero JA, Manaia A, Jimeno J, Lasky LL, Dieterlen-Lièvre F, Godin IE. 1998. Antigenic profiles of endothelial and hemopoietic lineages in murine intraembryonic hemogenic sites. Dev. Comp. Immunol. 22:303–19 [Google Scholar]
  36. Ge J, Li W, Zhao Q, Li N, Chen M. et al. 2015. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature 527:64–69 [Google Scholar]
  37. Ghaffari S, Leask RL, Jones EA. 2015a. Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis. Development 142:4151–57 [Google Scholar]
  38. Ghaffari S, Leask RL, Jones EA. 2015b. Simultaneous imaging of blood flow dynamics and vascular remodelling during development. Development 142:4158–67 [Google Scholar]
  39. Gibbons GH, Dzau VJ. 1994. The emerging concept of vascular remodeling. N. Engl. J. Med. 330:1431–38 [Google Scholar]
  40. Gimbrone MA Jr., Nagel T, Topper JN. 1997. Biomechanical activation: an emerging paradigm in endothelial adhesion biology. J. Clin. Investig. 99:1809–13 [Google Scholar]
  41. Gimbrone MA Jr., Topper JN, Nagel T, Anderson KR, García-Cardeña G. 2000. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann. N. Y. Acad. Sci. 902:230–39; discussion 239–40 [Google Scholar]
  42. Goetz JG, Steed E, Ferreira RR, Roth S, Ramspacher C. et al. 2014. Endothelial cilia mediate low flow sensing during zebrafish vascular development. Cell Rep 6:799–808 [Google Scholar]
  43. Gudi S, Nolan JP, Frangos JA. 1998. Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. PNAS 95:2515–19 [Google Scholar]
  44. Heckel E, Boselli F, Roth S, Krudewig A, Belting HG. et al. 2015. Oscillatory flow modulates mechanosensitive klf2a expression through trpv4 and trpp2 during heart valve development. Curr. Biol 25:1354–61 [Google Scholar]
  45. Helm CL, Fleury ME, Zisch AH, Boschetti F, Swartz MA. 2005. Synergy between interstitial flow and VEGF directs capillary morphogenesis in vitro through a gradient amplification mechanism. PNAS 102:15779–84 [Google Scholar]
  46. Henderson-Toth CE, Jahnsen ED, Jamarani R, Al-Roubaie S, Jones EA. 2012. The glycocalyx is present as soon as blood flow is initiated and is required for normal vascular development. Dev. Biol. 369:330–39 [Google Scholar]
  47. Hove JR, Koster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M. 2003. Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421:172–77 [Google Scholar]
  48. Ingber DE. 1993. Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J. Cell Sci. 104:Pt 3613–27 [Google Scholar]
  49. Jin ZG, Ueba H, Tanimoto T, Lungu AO, Frame MD, Berk BC. 2003. Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase. Circ. Res. 93:354–63 [Google Scholar]
  50. Jones EA, Baron MH, Fraser SE, Dickinson ME. 2005. Dynamic in vivo imaging of mammalian hematovascular development using whole embryo culture. Methods Mol. Med. 105:381–94 [Google Scholar]
  51. Jordan HE. 1917. Aortic cell clusters in vertebrate embryos. PNAS 3:149–56 [Google Scholar]
  52. Jung B, Obinata H, Galvani S, Mendelson K, Ding BS. et al. 2012. Flow-regulated endothelial S1P receptor–1 signaling sustains vascular development. Dev. Cell 23:600–10 [Google Scholar]
  53. Katta S, Krieg M, Goodman MB. 2015. Feeling force: physical and physiological principles enabling sensory mechanotransduction. Annu. Rev. Cell Dev. Biol. 31:347–71 [Google Scholar]
  54. Kazenwadel J, Betterman KL, Chong CE, Stokes PH, Lee YK. et al. 2015. GATA2 is required for lymphatic vessel valve development and maintenance. J. Clin. Investig. 125:2979–94 [Google Scholar]
  55. Kim PG, Nakano H, Das PP, Chen MJ, Rowe RG. et al. 2015. Flow-induced protein kinase A–CREB pathway acts via BMP signaling to promote HSC emergence. J. Exp. Med. 212:633–48 [Google Scholar]
  56. Knower HM. 1907. Effects of early removal of the heart and arrest of the circulation on the development of frog embryos. Anat. Rec. 7:161–65 [Google Scholar]
  57. Koslow AR, Stromberg RR, Friedman LI, Lutz RJ, Hilbert SL, Schuster P. 1986. A flow system for the study of shear forces upon cultured endothelial cells. J. Biomech. Eng. 108:338–41 [Google Scholar]
  58. Langille BL, O'Donnell F. 1986. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 231:405–7 [Google Scholar]
  59. Lansman JB, Hallam TJ, Rink TJ. 1987. Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers. ? Nature 325:811–13 [Google Scholar]
  60. Larina IV, Furushima K, Dickinson ME, Behringer RR, Larin KV. 2009. Live imaging of rat embryos with Doppler swept-source optical coherence tomography. J. Biomed. Opt 14050506 [Google Scholar]
  61. Larina IV, Sudheendran N, Ghosn M, Jiang J, Cable A. et al. 2008. Live imaging of blood flow in mammalian embryos using Doppler swept-source optical coherence tomography. J. Biomed. Opt 13060506 [Google Scholar]
  62. Lawson ND, Scheer N, Pham VN, Kim CH, Chitnis AB. et al. 2001. Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development 128:3675–83 [Google Scholar]
  63. Lawson ND, Vogel AM, Weinstein BM. 2002. sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Dev. Cell 3:127–36 [Google Scholar]
  64. le Noble F, Moyon D, Pardanaud L, Yuan L, Djonov V. et al. 2004. Flow regulates arterial-venous differentiation in the chick embryo yolk sac. Development 131:361–75 [Google Scholar]
  65. Lee JS, Yu Q, Shin JT, Sebzda E, Bertozzi C. et al. 2006. Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Dev. Cell 11:845–57 [Google Scholar]
  66. Levesque MJ, Nerem RM. 1985. The elongation and orientation of cultured endothelial cells in response to shear stress. J. Biomech. Eng. 107:341–47 [Google Scholar]
  67. Li J, Hou B, Tumova S, Muraki K, Bruns A. et al. 2014. Piezo1 integration of vascular architecture with physiological force. Nature 515:279–82 [Google Scholar]
  68. Lin K, Hsu PP, Chen BP, Yuan S, Usami S. et al. 2000. Molecular mechanism of endothelial growth arrest by laminar shear stress. PNAS 97:9385–89 [Google Scholar]
  69. Loeb J. 1893. Uber die Entwicklung von Fischembryonen ohne Kreislauf. Arch. Gesamte Physiol. Menschen Tiere 54:525–31 [Google Scholar]
  70. Lucitti JL, Jones EA, Huang C, Chen J, Fraser SE, Dickinson ME. 2007. Vascular remodeling of the mouse yolk sac requires hemodynamic force. Development 134:3317–26 [Google Scholar]
  71. Mazzag BM, Tamaresis JS, Barakat AI. 2003. A model for shear stress sensing and transmission in vascular endothelial cells. Biophys. J. 84:4087–101 [Google Scholar]
  72. Mochizuki S, Vink H, Hiramatsu O, Kajita T, Shigeto F. et al. 2003. Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release. Am. J. Physiol. Heart Circ. Physiol. 285:H722–26 [Google Scholar]
  73. Moore JE Jr., Burki E, Suciu A, Zhao S, Burnier M. et al. 1994. A device for subjecting vascular endothelial cells to both fluid shear stress and circumferential cyclic stretch. Ann. Biomed. Eng 22416–22 [Google Scholar]
  74. Moyon D, Pardanaud L, Yuan L, Breant C, Eichmann A. 2001. Plasticity of endothelial cells during arterial-venous differentiation in the avian embryo. Development 128:3359–70 [Google Scholar]
  75. Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND. 2010. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature 464:1196–200 [Google Scholar]
  76. North TE, de Bruijn MF, Stacy T, Talebian L, Lind E. et al. 2002. Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 16:661–72 [Google Scholar]
  77. North TE, Goessling W, Peeters M, Li P, Ceol C. et al. 2009. Hematopoietic stem cell development is dependent on blood flow. Cell 137:736–48 [Google Scholar]
  78. Osawa M, Masuda M, Kusano K, Fujiwara K. 2002. Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction: Is it a mechanoresponsive molecule. ? J. Cell Biol. 158:773–85 [Google Scholar]
  79. Park H, Go YM, Darji R, Choi JW, Lisanti MP. et al. 2000. Caveolin-1 regulates shear stress–dependent activation of extracellular signal–regulated kinase. Am. J. Physiol. Heart Circ. Physiol. 278:H1285–93 [Google Scholar]
  80. Parmar KM, Larman HB, Dai G, Zhang Y, Wang ET. et al. 2006. Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J. Clin. Investig. 116:49–58 [Google Scholar]
  81. Planas-Paz L, Strilic B, Goedecke A, Breier G, Fassler R, Lammert E. 2012. Mechanoinduction of lymph vessel expansion. EMBO J 31:788–804 [Google Scholar]
  82. Ranade SS, Qiu Z, Woo SH, Hur SS, Murthy SE. et al. 2014. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. PNAS 111:10347–52 [Google Scholar]
  83. Rizzo V, McIntosh DP, Oh P, Schnitzer JE. 1998. In situ flow activates endothelial nitric oxide synthase in luminal caveolae of endothelium with rapid caveolin dissociation and calmodulin association. J. Biol. Chem. 273:34724–29 [Google Scholar]
  84. Roux W. 1878. Über die Verzweigungen der Blutgefäße des Menschen. Jena. Z. Naturw. 12:205–6 [Google Scholar]
  85. Rubanyi GM. 1991. Ionic mechanisms involved in the flow- and pressure-sensor function of the endothelium. Z. Kardiol. 80:Suppl. 791–94 [Google Scholar]
  86. Sabin FR. 1909. The lymphatic system in human embryos, with a consideration of the morphology of the system as a whole. Am. J. Anat. 9:143–91 [Google Scholar]
  87. Sabin FR. 1917. Preliminary note on the differentiation of angioblasts and the method by which they produce blood-vessels, blood-plasma and red blood-cells as seen in the living chick. Anat. Rec. 13:199–204 [Google Scholar]
  88. Sabine A, Agalarov Y, Maby-El Hajjami H, Jaquet M, Hagerling R. et al. 2012. Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Dev. Cell 22:430–45 [Google Scholar]
  89. Serluca FC, Drummond IA, Fishman MC. 2002. Endothelial signaling in kidney morphogenesis: a role for hemodynamic forces. Curr. Biol. 12:492–97 [Google Scholar]
  90. Shay-Salit A, Shushy M, Wolfovitz E, Yahav H, Breviario F. et al. 2002. VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells. PNAS 99:9462–67 [Google Scholar]
  91. Shin D, García-Cardeña G, Hayashi S, Gerety S, Asahara T. et al. 2001. Expression of ephrinB2 identifies a stable genetic difference between arterial and venous vascular smooth muscle as well as endothelial cells, and marks subsets of microvessels at sites of adult neovascularization. Dev. Biol. 230:139–50 [Google Scholar]
  92. Siegel G, Malmsten M, Klussendorf D, Walter A, Schnalke F, Kauschmann A. 1996. Blood-flow sensing by anionic biopolymers. J. Auton. Nerv. Syst. 57:207–13 [Google Scholar]
  93. Smith RA, Glomski CA. 1982. “Hemogenic endothelium” of the embryonic aorta: Does it exist?. Dev. Comp. Immunol. 6:359–68 [Google Scholar]
  94. Stockard CR. 1915. The origin of blood and vascular endothelium in embryos without a circulation of the blood and in the normal embryo. Am. J. Anat. 18:227–327 [Google Scholar]
  95. Steed E, Boselli F, Vermot J. 2016. Hemodynamics driven cardiac valve morphogenesis. Biochim. Biophys. Acta. 1863:71760–66 [Google Scholar]
  96. Sweet DT, Jimenez JM, Chang J, Hess PR, Mericko-Ishizuka P. et al. 2015. Lymph flow regulates collecting lymphatic vessel maturation in vivo. J. Clin. Investig. 125:2995–3007 [Google Scholar]
  97. Swift MR, Weinstein BM. 2009. Arterial-venous specification during development. Circ. Res. 104:576–88 [Google Scholar]
  98. Tabas I, García-Cardeña G, Owens GK. 2015. Recent insights into the cellular biology of atherosclerosis. J. Cell Biol. 209:13–22 [Google Scholar]
  99. Thoma R. 1896. Textbook of General Pathology and Pathological Anatomy London: Adam and Charles Black [Google Scholar]
  100. Traub O, Ishida T, Ishida M, Tupper JC, Berk BC. 1999. Shear stress–mediated extracellular signal–regulated kinase activation is regulated by sodium in endothelial cells. Potential role for a voltage-dependent sodium channel. J. Biol. Chem. 274:20144–50 [Google Scholar]
  101. Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA. et al. 2005. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437:426–31 [Google Scholar]
  102. Vermot J, Forouhar AS, Liebling M, Wu D, Plummer D. et al. 2009. Reversing blood flows act through klf2a to ensure normal valvulogenesis in the developing heart. PLOS Biol 7:e1000246 [Google Scholar]
  103. Wang HU, Chen ZF, Anderson DJ. 1998. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93:741–53 [Google Scholar]
  104. Wang L, Zhang P, Wei Y, Gao Y, Patient R, Liu F. 2011. A blood flow–dependent klf2a-NO signaling cascade is required for stabilization of hematopoietic stem cell programming in zebrafish embryos. Blood 118:4102–10 [Google Scholar]
  105. Wang N, Tytell JD, Ingber DE. 2009. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat. Rev. Mol. Cell Biol. 10:75–82 [Google Scholar]
  106. Wang Y, Miao H, Li S, Chen KD, Li YS. et al. 2002. Interplay between integrins and FLK-1 in shear stress–induced signaling. Am. J. Physiol. Cell Physiol. 283:C1540–47 [Google Scholar]
  107. Wang Y, Simons M. 2014. Flow-regulated lymphatic vasculature development and signaling. Vasc. Cell 6:14 [Google Scholar]
  108. Zhong TP, Childs S, Leu JP, Fishman MC. 2001. Gridlock signalling pathway fashions the first embryonic artery. Nature 414:216–20 [Google Scholar]
  109. Zhong TP, Rosenberg M, Mohideen MA, Weinstein B, Fishman MC. 2000. gridlock, an HLH gene required for assembly of the aorta in zebrafish. Science 287:1820–24 [Google Scholar]
  110. Zovein AC, Hofmann JJ, Lynch M, French WJ, Turlo KA. et al. 2008. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 3:625–36 [Google Scholar]

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