Skip to main content
SpringerLink
Log in

VEGF and Endothelial Guidance in Angiogenic Sprouting

  • Chapter
VEGF in Development

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

The cellular actions of VEGF need to be coordinated to guide vascular patterning during sprouting angiogenesis. Individual endothelial tip cells lead and guide the blood vessel sprout, while neighbouring stalk cells proliferate and form the vascular lumen. Recent studies illustrate how endothelial DLL4/NOTCH signalling, stimulated by VEGF, regulates the sprouting response by limiting tip cell formation in the stalk. The spatial distribution of VEGF, in turn, regulates the shape of the ensuing sprout by directing tip cell migration and determining stalk cell proliferation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Risau W. Mechanisms of angiogenesis. Nature 1997; 386:671–674.

    Article  PubMed  CAS  Google Scholar 

  2. Ruhrberg C. Growing and shaping the vascular tree: Multiple roles for VEGF. Bioessays 2003; 25(11):1052–1060.

    Article  PubMed  CAS  Google Scholar 

  3. Metzger RJ, Krasnow MA. Genetic control of branching morphogenesis. Science 1999; 284(5420):1635–1639.

    Article  PubMed  CAS  Google Scholar 

  4. Ghabrial AS, Krasnow MA. Social interactions among epithelial cells during tracheal branching morphogenesis. Nature 2006; 441(7094):746–749.

    Article  PubMed  CAS  Google Scholar 

  5. Ribeiro C, Ebner A, Affolter M. In vivo imaging reveals different cellular functions for FGF and Dpp signaling in tracheal branching morphogenesis. Dev Cell 2002; 2(5):677–683.

    Article  PubMed  CAS  Google Scholar 

  6. Bar T, Wolff JR. The formation of capillary basement membranes during internal vascularization of the rat’s cerebral cortex. Z Zellforsch 1972; 133:231–248.

    Article  PubMed  CAS  Google Scholar 

  7. Mato M, Ookawara S. Ultrastructural observation on the tips of growing vascular cords in the rat cerebral cortex. Experientia 1982; 38(4):499–501.

    Article  PubMed  CAS  Google Scholar 

  8. Marin-Padilla M. Early vascularization of the embryonic cerebral cortex: Golgi and electron microscopic studies. J Comp Neurol 1985; 241(2):237–249.

    Article  PubMed  CAS  Google Scholar 

  9. Leung DW, Cachianes G, Kuang WJ et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246(4935):1306–1309.

    Article  PubMed  CAS  Google Scholar 

  10. Gerhardt H, Golding M, Fruttiger M et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 2003; 161(6):1163–1177.

    Article  PubMed  CAS  Google Scholar 

  11. Ruhrberg C, Gerhardt H, Golding M et al. Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev 2002; 16(20):2684–2698.

    Article  PubMed  CAS  Google Scholar 

  12. Mato M, Ookawara S, Namiki T. Studies on the vasculogenesis in rat cerebral cortex. Anat Rec 1989; 224(3):355–364.

    Article  PubMed  CAS  Google Scholar 

  13. Flamme I, Baranowski A, Risau W. A new model of vasculogenesis and angiogenesis in vitro as compared with vascular growth in the avian area vasculosa. Anat Rec 1993; 237(1):49–57.

    Article  PubMed  CAS  Google Scholar 

  14. Kurz H, Gartner T, Eggli PS et al. First blood vessels in the avian neural tube are formed by a combination of dorsal angioblast immigration and ventral sprouting of endothelial cells. Dev Biol 1996; 173(1):133–147.

    Article  PubMed  CAS  Google Scholar 

  15. Breier G, Risau W. The role of vascular endothelial growth factor in blood vessel formation. Trends in Cell Biol 1996; 6:454–456.

    Article  CAS  Google Scholar 

  16. Ausprunk DH, Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 1977; 14(1):53–65.

    Article  PubMed  CAS  Google Scholar 

  17. Fruttiger M. Development of the retinal vasculature. Angiogenesis 2007; 10(2):77–88.

    Article  PubMed  Google Scholar 

  18. Uemura A, Kusuhara S, Katsuta H et al. Angiogenesis in the mouse retina: A model system for experimental manipulation. Exp Cell Res 2006; 312(5):676–683.

    Article  PubMed  CAS  Google Scholar 

  19. Fruttiger M, Calver AR, Kruger WH et al. PDGF mediates a neuron-astrocyte interaction in the developing retina. Neuron 1996; 17(6):1117–1131.

    Article  PubMed  CAS  Google Scholar 

  20. Dorrell MI, Aguilar E, Friedlander M. Retinal vascular development is mediated by endothelial filopodia, a preexisting astrocytic template and specific R-cadherin adhesion. Invest Ophthalmol Vis Sci 2002; 43(11):3500–3510.

    PubMed  Google Scholar 

  21. West H, Richardson WD, Fruttiger M. Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes. Development 2005; 132(8):1855–1862.

    Article  PubMed  CAS  Google Scholar 

  22. Goldstein GW. Endothelial cell-astrocyte interactions: A cellular model of the blood-brain barrier. Ann NY Acad Sci 1988; 529:31–39.

    Article  PubMed  CAS  Google Scholar 

  23. Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006; 7(1):41–53.

    Article  PubMed  CAS  Google Scholar 

  24. Provis JM, Leech J, Diaz CM et al. Development of the human retinal vasculature: Cellular relations and VEGF expression. Exp Eye Res 1997; 65:555–568.

    Article  PubMed  CAS  Google Scholar 

  25. Stone J, Itin A, Alon T et al. Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growtn factor (VEGF) expression by neuroglia. J Neurosci 1995; 15:4738–4747.

    PubMed  CAS  Google Scholar 

  26. Kearney JB, Kappas NC, Ellerstrom C et al. The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood 2004; 103(12):4527–4535.

    Article  PubMed  CAS  Google Scholar 

  27. Claxton S, Fruttiger M. Oxygen modifies artery differentiation and network morphogenesis in the retinal vasculature. Dev Dyn 2005; 233(3):822–828.

    Article  PubMed  CAS  Google Scholar 

  28. Zeng G, Taylor SM, McColm JR et al. Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation. Blood 2007; 109(4): 1345–1352.

    Article  PubMed  CAS  Google Scholar 

  29. Kearney JB, Ambler CA, Monaco KA et al. Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. Blood 2002; 99(7):2397–2407.

    Article  PubMed  CAS  Google Scholar 

  30. McCue S, Dajnowiec D, Xu F et al. Shear stress regulates forward and reverse planar cell polarity of vascular endothelium in vivo and in vitro. Circ Res 2006; 98(7):939–946.

    Article  PubMed  CAS  Google Scholar 

  31. Shutter JR, Scully S, Fan W et al. D114, a novel Notch ligand expressed in arterial endothelium. Genes Dev 2000; 14(11):1313–1318.

    PubMed  CAS  Google Scholar 

  32. Claxton S, Fruttiger M. Periodic Delta-like 4 expression in developing retinal arteries. Gene Expr Patterns 2004; 5(1):123–127.

    Article  PubMed  CAS  Google Scholar 

  33. Gale NW, Dominguez MG, Noguera I et al. Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development. Proc Natl Acad Sci USA 2004; 101(45):15949–15954.

    Article  PubMed  CAS  Google Scholar 

  34. Krebs LT, Shutter JR, Tanigaki K et al. Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev 2004; 18(20):2469–2473.

    Article  PubMed  CAS  Google Scholar 

  35. Duarte A, Hirashima M, Benedito R et al. Dosage-sensitive requirement for mouse D114 in artery development. Genes Dev 2004; 18(20):2474–2478.

    Article  PubMed  CAS  Google Scholar 

  36. Sainson RC, Aoto J, Nakatsu MN et al. Cell-autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis. FASEB J 2005; 19(8): 1027–1029.

    PubMed  CAS  Google Scholar 

  37. Hellstrom M, Phng LK, Hofmann JJ et al. DU4 signalling through Notchl regulates formation of tip cells during angiogenesis. Nature 2007; 445(7129):776–780.

    Article  PubMed  CAS  Google Scholar 

  38. Leslie JD, Ariza-McNaughton L, Bermange AL et al. Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis. Development 2007; 134(5):839–844.

    Article  PubMed  CAS  Google Scholar 

  39. Lobov IB, Renard RA, Papadopoulos N et al. Delta-like ligand 4 (DU4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc Natl Acad Sci USA 2007; 104(9):3219–3224.

    Article  PubMed  CAS  Google Scholar 

  40. Siekmann AF, Lawson ND. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature 2007; 445(7129):781–784.

    Article  PubMed  CAS  Google Scholar 

  41. Suchting S, Freitas C, le Noble F et al. The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc Natl Acad Sci USA 2007; 104(9):3225–3230.

    Article  PubMed  CAS  Google Scholar 

  42. Liu ZJ, Shirakawa T, Li Y et al. Regulation of Notchl and D114 by vascular endothelial growth factor in arterial endothelial cells: Implications for modulating arteriogenesis and angiogenesis. Mol Cell Biol 2003; 23(1):14–25.

    Article  PubMed  CAS  Google Scholar 

  43. Berezovska O, Jack C, McLean P et al. Rapid Notchl nuclear translocation after ligand binding depends on presenilin-associated gamma-secretase activity. Ann N Y Acad Sci 2000; 920:223–226.

    Article  PubMed  CAS  Google Scholar 

  44. De Strooper B, Annaert W, Cupers P et al. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 1999; 398(6727):518–522.

    Article  PubMed  CAS  Google Scholar 

  45. Ehebauer M, Hayward P, Martinez-Arias A. Notch signaling pathway. Sci STKE 2006; 2006(364):cm7.

    Google Scholar 

  46. Iso T, Kedes L, Hamamori Y. HES and HERP families: Multiple effectors of the Notch signaling pathway. J Cell Physiol 2003; 194(3):237–255.

    Article  PubMed  CAS  Google Scholar 

  47. Noguera-Troise I, Daly C, Papadopoulos NJ et al. Blockade of D114 inhibits tumour growth by promoting non-productive angiogenesis. Nature 2006; 444(7122): 1032–1037.

    Article  PubMed  CAS  Google Scholar 

  48. Ridgway J, Zhang G, Wu Y et al. Inhibition of D114 signalling inhibits tumour growth by deregulating angiogenesis. Nature 2006; 444(7122): 1083–1087.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vascular Biology Laboratory, Cancer Research UK, London Research Institute, Lincoln’s Inn Fields Laboratories, 44 Lincoln’s Inn Fields, London, WC2A 3PX, UK

    Holger Gerhardt

Authors
  1. Holger Gerhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Gerhardt, H. (2008). VEGF and Endothelial Guidance in Angiogenic Sprouting. In: VEGF in Development. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78632-2_6

Download citation

Publish with us

Policies and ethics

Search

Navigation