Molecular regulation of angiogenesis and lymphangiogenesis

Nature Reviews Molecular Cell Biology

Volumn 8, Issue 6, 2007, Pages 464-478

  Adams, Ralf H ^a   Alitalo, Kari ^b  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^b UNIVERSITY OF HELSINKI   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPOIETIN; ANGIOPOIETIN RECEPTOR; BIOLOGICAL MARKER; CELL ADHESION MOLECULE; COLLAGEN TYPE 4; EPHRIN; EPHRIN B2; EPHRIN B4; G PROTEIN COUPLED RECEPTOR; LYMPHATIC ENDOTHELIAL HYALURONAN RECEPTOR 1; NETRIN; NEUROPILIN 1; PLACENTAL GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PODOPLANIN; PROSPERO RELATED HOMEOBOX 1 PROTEIN; SECONDARY LYMPHOID TISSUE CHEMOKINE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NR2F2; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG; VASCULOTROPIN A; VASCULOTROPIN B; VASCULOTROPIN C; VASCULOTROPIN D; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3;

ANGIOGENESIS; CELL COMMUNICATION; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CHEMOTAXIS; EMBRYO DEVELOPMENT; EXTRACELLULAR MATRIX; HUMAN; LYMPHANGIOGENESIS; MOLECULAR DYNAMICS; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; TISSUE SPECIFICITY;

ANIMALS; BIOLOGICAL MARKERS; BLOOD VESSELS; CELL DIFFERENTIATION; HUMANS; LYMPHANGIOGENESIS; LYMPHATIC VESSELS; MODELS, BIOLOGICAL; NEOVASCULARIZATION, PHYSIOLOGIC;

VERTEBRATA;

EID: 34249689753     PISSN: 14710072     EISSN: 14710080     Source Type: Journal    
DOI: 10.1038/nrm2183     Document Type: Review

References (149)

1. Carmeliet, P. Angiogenesis in health and disease. Nature Med. 9, 653-660 (2003).
2. Cueni, L. N. & Detmar, M. New insights into the molecular control of the lymphatic vascular system and its role in disease. J. Invest. Dermatol. 126, 2167-2177 (2006).
3. Jain, R. K. Molecular regulation of vessel maturation. Nature Med. 9, 685-693 (2003).
4. Alitalo, K., Tammela, T. & Petrova, T. V. Lymphangiogenesis in development and human disease. Nature 438, 946-953 (2005).
5. He, Y. et al. Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res. 65, 4739-4746 (2005).
6. Achen, M. G. & Stacker, S. A. Tumor lymphangiogenesis and metastatic spread - new players begin to emerge. Int. J. Cancer 119, 1755-1760 (2006).
7. Shibuya, M. Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis. J. Biochem. Mol. Biol. 39, 469-478 (2006).
8. Ferrara, N., Gerber, H. P. & LeCouter, J. The biology of VEGF and its receptors. Nature Med. 9, 669-676 (2003).
9. Ladomery, M. R., Harper, S. J. & Bates, D. O. Alternative splicing in angiogenesis: the vascular endothelial growth factor paradigm. Cancer Lett. 249, 133-142 (2006).
10. Nyberg, P., Xie, L. & Kalluri, R. Endogenous inhibitors of angiogenesis. Cancer Res. 65, 3967-3979 (2005).
11. Lee, S., Jilani, S. M., Nikolova, G. V., Carpizo, D. & Iruela-Arispe, M. L. Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J. Cell Biol. 169, 681-691 (2005).
12. Armulik, A., Abramsson, A. & Betsholtz, C. Endothelial/pericyte interactions. Circ. Res. 97, 512-523 (2005).
13. Bergers, G. & Song, S. The role of pericytes in bloodvessel formation and maintenance. Neuro-oncology 7, 452-464 (2005).
14. Sainson, R. C. et al. Cell-autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis. FASEB J. 19, 1027-1029 (2005).
15. Hellstrom, M. et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 445, 776-780 (2007). One of several papers, which shows that endothelial sprouting and the selection of tip cells in the developing mouse retina are controlled by DLL4-Notch signalling.
16. Ridgway, J. et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 444, 1083-1087 (2006).
17. Noguera-Troise, I. et al. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444, 1032-1037 (2006). References 16 and 17 demonstrate that blocking of DLL4-mediated signalling dramatically enhances angiogenic sprouting of tumour blood vessels. This process leads to compromised vessel formation, increased hypoxia and reduced tumour growth.
18. Lobov, I. B. et al. Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc. Natl Acad. Sci. USA 104, 3219-3224 (2007).
19. Suchting, S. et al. The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc. Natl Acad. Sci. USA 104, 3225-3230 (2007).
20. Leslie, J. D. et al. Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis. Development 134, 839-844 (2007).
21. Siekmann, A. F. & Lawson, N. D. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature 445, 781-784 (2007). References 20 and 21 show that Notch signalling by Dll4 controls the angiogenic behaviour of endothelial cells in zebrafish intersegmental vessels.
22. Ruhrberg, C. et al. Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev. 16, 2684-2698 (2002).
23. Gerhardt, H. et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J. Cell Biol. 161, 1163-1177 (2003). Characterization of the endothelial tip cell in the retina and the role of matrix-bound VEGF gradients in the guidance of vascular sprouts.
24. Klagsbrun, M., Takashima, S. & Mamluk, R. The role of neuropilin in vascular and tumor biology. Adv. Exp. Med. Biol. 515, 33-48 (2002).
25. Neufeld, G. et al. The neuropilins: multifunctional semaphorin and VEGF receptors that modulate axon guidance and angiogenesis. Trends Cardiovasc. Med. 12, 13-19 (2002).
26. Pan, Q. et al. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 11, 53-67 (2007).
27. Gerhardt, H. et al. Neuropilin-1 is required for endothelial tip cell guidance in the developing central nervous system. Dev. Dyn. 231, 503-509 (2004).
28. Carmeliet, P. & Tessier-Lavigne, M. Common mechanisms of nerve and blood vessel wiring. Nature 436, 193-200 (2005).
29. Eichmann, A., Makinen, T. & Alitalo, K. Neural guidance molecules regulate vascular remodeling and vessel navigation. Genes Dev. 19, 1013-1021 (2005).
30. Kruger, R. P., Aurandt, J. & Guan, K. L. Semaphorins command cells to move. Nature Rev. Mol. Cell Biol. 6, 789-800 (2005).
31. Neufeld, G. et al. Semaphorins in cancer. Front. Biosci. 10, 751-760 (2005).
32. Gu, C. et al. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science 307, 265-268 (2005).
33. Gitler, A. D., Lu, M. M. & Epstein, J. A. PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development. Dev. Cell 7, 107-116 (2004).
34. Torres-Vazquez, J. et al. Semaphorin-plexin signaling guides patterning of the developing vasculature. Dev. Cell 7, 117-123 (2004).
35. Lu, X. et al. The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 432, 179-186 (2004). Identification of UNC5B as a guidance receptor that controls vascular sprouting, which is reminiscent of the role of UNC5 molecules in the pathfinding of axonal growth cones.
36. Wilson, B. D. et al. Netrins promote developmental and therapeutic angiogenesis. Science 313, 640-644 (2006).
37. Bedell, V. M. et al. roundabout4 is essential for angiogenesis in vivo. Proc. Natl Acad. Sci. USA 102, 6373-6378 (2005).
38. Park, K. W. et al. Robo4 is a vascular-specific receptor that inhibits endothelial migration. Dev. Biol. 261, 251-267 (2003).
39. Suchting, S., Heal, P., Tahtis, K., Stewart, L. M. & Bicknell, R. Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration. FASEB J. 19, 121-123 (2005).
40. Kamei, M. et al. Endothelial tubes assemble from intracellular vacuoles in vivo. Nature 442, 453-456 (2006). Beautiful demonstration that the lumen of endothelial cells in zebrafish intersegmental vessels is formed through the fusion of intracellular vacuoles. This is followed by intercellular fusion processes.
41. Lubarsky, B. & Krasnow, M. A. Tube morphogenesis: making and shaping biological tubes. Cell 112, 19-28 (2003).
42. Davis, G. E. & Bayless, K. J. An integrin and Rho GTPase-dependent pinocytic vacuole mechanism controls capillary lumen formation in collagen and fibrin matrices. Microcirculation 10, 27-44 (2003).
43. Parker, L. H. et al. The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature 428, 754-758 (2004).
44. Mancuso, M. R. et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J. Clin. Invest. 116, 2610-2621 (2006).
45. Cleaver, O. & Melton, D. A. Endothelial signaling during development. Nature Med. 9, 661-668 (2003).
46. Rafii, S., Lyden, D., Benezra, R., Hattori, K. & Heissig, B. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nature Rev. Cancer 2, 826-835 (2002).
47. Grunewald, M. et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 124, 175-189 (2006). Demonstration that the recruitment of perivascular bone-marrow-derived circulating cells has an important role in adult angiogenesis.
48. Djonov, V. & Makanya, A. N. New insights into intussusceptive angiogenesis. EXS 17-33 (2005).
49. Torres-Vazquez, J., Kamei, M. & Weinstein, B. M. Molecular distinction between arteries and veins. Cell Tissue Res. 314, 43-59 (2003).
50. Heil, M., Eitenmuller, I., Schmitz-Rixen, T. & Schaper, W. Arteriogenesis versus angiogenesis: similarities and differences. J. Cell. Mol. Med. 10, 45-55 (2006).
51. Brouillard, P. & Vikkula, M. Vascular malformations: localized defects in vascular morphogenesis. Clin. Genet. 63, 340-351 (2003).
52. Bergan, J. J. et al. Chronic venous disease. N. Engl. J. Med. 355, 488-498 (2006).
53. Le Borgne, R., Bardin, A. & Schweisguth, F. The roles of receptor and ligand endocytosis in regulating Notch signaling. Development 132, 1751-1762 (2005).
54. Bray, S. J. Notch signalling: a simple pathway becomes complex. Nature Rev. Mol. Cell Biol. 7, 678-689 (2006).
55. Limbourg, F. P. et al. Essential role of endothelial Notch1 in angiogenesis. Circulation 111, 1826-1832 (2005).
56. Krebs, L. T. et al. Notch signaling is essential for vascular morphogenesis in mice. Genes Dev. 14, 1343-1352 (2000).
57. Koo, B. K. et al. Mind bomb 1 is essential for generating functional Notch ligands to activate Notch. Development 132, 3459-3470 (2005).
58. Fischer, A., Schumacher, N., Maier, M., Sendtner, M. & Gessler, M. The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev. 18, 901-911 (2004).
59. Krebs, L. T. et al. Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev. 18, 2469-2473 (2004).
60. Gale, N. W. 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 101, 15949-15954 (2004).
61. Duarte, A. et al. Dosage-sensitive requirement for mouse Dll4 in artery development. Genes Dev. 18, 2474-2478 (2004).
62. Nakajima, M. et al. Abnormal blood vessel development in mice lacking presenilin-1. Mech. Dev. 120, 657-667 (2003).
63. Himanen, J. P. & Nikolov, D. B. Eph receptors and ephrins. Int. J. Biochem. Cell Biol. 35, 130-134 (2003).
64. Murai, K. K. & Pasquale, E. B. 'Eph'ective signaling: forward, reverse and crosstalk. J. Cell Sci. 116, 2823-2832 (2003).
65. Williams, C. K., Li, J. L., Murga, M., Harris, A. L. & Tosato, G. Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function. Blood 107, 931-939 (2006).
66. Hainaud, P. et al. The role of the vascular endothelial growth factor-Delta-like 4 ligand/Notch4-Ephrin b2 cascade in tumor vessel remodeling and endothelial cell functions. Cancer Res. 66, 8501-8510 (2006).
67. Mukouyama, Y. S., Gerber, H. P., Ferrara, N., Gu, C. & Anderson, D. J. Peripheral nerve-derived VEGF promotes arterial differentiation via neuropilin1-mediated positive feedback. Development 132, 941-52 (2005).
68. Yuan, L. et al. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 129, 4797-4806 (2002).
69. Stalmans, I. et al. Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J. Clin. Invest. 109, 327-336 (2002).
70. Gu, C. et al. Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev. Cell 5, 45-57 (2003).
71. Jakobsson, L. et al. Heparan sulfate in trans potentiates VEGFR-mediated angiogenesis. Dev. Cell 10, 625-634 (2006).
72. Kwei, S. et al. Early adaptive responses of the vascular wall during venous arterialization in mice. Am. J. Pathol. 164, 81-89 (2004).
73. le Noble, F. et al. Flow regulates arterial-venous differentiation in the chick embryo yolk sac. Development 131, 361-375 (2004).
74. You, L. R. et al. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature 435, 98-104 (2005). Shows that the nuclear orphan receptor COUP-TFII suppresses the expression of components of the Notch pathway in venous endothelial cells. Because Notch signalling controls arterial differentiation, COUP-TFII is crucial for the specification of arteriovenous identity.
75. Seo, S. et al. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev. Biol. 294, 458-470 (2006).
76. LeCouter, J. et al. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412, 877-884 (2001).
77. Oliver, G. Lymphatic vasculature development. Nature Rev. Immunol. 4, 35-45 (2004).
78. Oliver, G. & Alitalo, K. The lymphatic vasculature: recent progress and paradigms. Annu. Rev. Cell Dev. Biol. 21, 457-483 (2005).
79. Petrova, T. V. et al. Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J. 21, 4593-4599 (2002).
80. Wilting, J. et al. Dual origin of avian lymphatics. Dev. Biol. 292, 165-173 (2006).
81. Sebzda, E. et al. Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development. Dev. Cell 11, 349-361 (2006).
82. Hong, Y. K. et al. Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev. Dyn. 225, 351-357 (2002).
83. Wigle, J. T. et al. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 21, 1505-1513 (2002).
84. Wigle, J. T. & Oliver, G. Prox1 function is required for the development of the murine lymphatic system. Cell 98, 769-778 (1999). Identification of PROX1 as the regulator of the first steps of lymphangiogenic growth in the mouse embryo.
85. Harvey, N. L. et al. Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adultonset obesity. Nature Genet. 37, 1072-1081 (2005).
86. Backhed, F., Crawford, P. A., O'Donnell, D. & Gordon, J. I. Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor. Proc. Natl Acad. Sci. USA 104, 606-611 (2007).
87. Abtahian, F. et al. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 299, 247-251 (2003).
88. Karkkainen, M. J. et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nature Immunol. 5, 74-80 (2004). Demonstration that the sprouting of PROX1-expressing lymphatic endothelial cells from embryonic veins is controlled by VEGFC.
89. Baldwin, M. E. et al. Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Mol. Cell. Biol. 25, 2441-2449 (2005).
90. Tammela, T., Enholm, B., Alitalo, K. & Paavonen, K. The biology of vascular endothelial growth factors. Cardiovasc. Res. 65, 550-563 (2005).
91. Ober, E. A. et al. Vegfc is required for vascular development and endoderm morphogenesis in zebrafish. EMBO Rep. 5, 78-84 (2004).
92. Dumont, D. J. et al. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science 282, 946-949 (1998).
93. Karpanen, T. et al. Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation. Am. J. Pathol. 169, 708-718 (2006).
94. Makinen, T. et al. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nature Med. 7, 199-205 (2001).
95. Laakkonen, P. et al. Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis and growth. Cancer Res. 67, 593-599 (2007).
96. Karpanen, T. et al. Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. FASEB J. 20, 1462-72 (2006).
97. Nagy, J. A. et al. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J. Exp. Med. 196, 1497-1506 (2002).
98. Hong, Y. K. et al. VEGF-A promotes tissue repairassociated lymphatic vessel formation via VEGFR-2 and the α1β1 and α2β1 integrins. FASEB J. 18, 1111-1113 (2004).
99. Hirakawa, S. et al. VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J. Exp. Med. 201, 1089-1099 (2005).
100. Baluk, P. et al. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J. Clin. Invest. 115, 247-257 (2005).
101. Cursiefen, C. et al. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J. Clin. Invest. 113, 1040-1050 (2004).
102. Gale, N. W. et al. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev. Cell 3, 411-423 (2002).
103. Tammela, T. et al. Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Blood 105, 4642-4648 (2005).
104. Makinen, T. et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev. 19, 397-410 (2005).
105. Foo, S. S. et al. Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly. Cell 124, 161-173 (2006).
106. Fang, J. et al. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am. J. Hum. Genet. 67, 1382-1388 (2000).
107. Kriederman, B. M. et al. FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome. Hum. Mol. Genet. 12, 1179-1185 (2003).
108. Petrova, T. V. et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nature Med. 10, 974-981 (2004).
109. Baluk, P., Hashizume, H. & McDonald, D. M. Cellular abnormalities of blood vessels as targets in cancer. Curr. Opin. Genet. Dev. 15, 102-111 (2005).
110. Jain, R. K. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307, 58-62 (2005).
111. Betsholtz, C., Lindblom, P. & Gerhardt, H. Role of pericytes in vascular morphogenesis. EXS 115-125 (2005).
112. Rolny, C. et al. Platelet-derived growth factor receptor-β promotes early endothelial cell differentiation. Blood 108, 1877-1886 (2006).
113. Allende, M. L. & Proia, R. L. Sphingosine-1-phosphate receptors and the development of the vascular system. Biochim. Biophys. Acta 1582, 222-227 (2002).
114. Spiegel, S. & Milstien, S. Sphingosine-1-phosphate: an enigmatic signalling lipid. Nature Rev. Mol. Cell Biol. 4, 397-407 (2003).
115. Kono, M. et al. The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis. J. Biol. Chem. 279, 29367-29373 (2004).
116. Liu, Y. et al. Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J. Clin. Invest. 106, 951-961 (2000).
117. Allende, M. L., Yamashita, T. & Proia, R. L. G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation. Blood 102, 3665-3667 (2003).
118. Paik, J. H. et al. Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Genes Dev. 18, 2392-2403 (2004).
119. Luo, Y. & Radice, G. L. N-cadherin acts upstream of VE-cadherin in controlling vascular morphogenesis. J. Cell Biol. 169, 29-34 (2005).
120. Chen, S. & Lechleider, R. J. Transforming growth factor-β- induced differentiation of smooth muscle from a neural crest stem cell line. Circ. Res. 94, 1195-1202 (2004).
121. Pipes, G. C., Creemers, E. E. & Olson, E. N. The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis. Genes Dev. 20, 1545-1556 (2006).
122. Miano, J. M. et al. Restricted inactivation of serum response factor to the cardiovascular system. Proc. Natl Acad. Sci. USA 101, 17132-17137 (2004).
123. Nishimura, G. et al. δEF1 mediates TGF-β signaling in vascular smooth muscle cell differentiation. Dev. Cell 11, 93-104 (2006).
124. Chang, D. F. et al. Cysteine-rich LIM-only proteins CRP1 and CRP2 are potent smooth muscle differentiation cofactors. Dev. Cell 4, 107-118 (2003).
125. Bertolino, P., Deckers, M., Lebrin, F. & ten Dijke, P. Transforming growth factor-β signal transduction in angiogenesis and vascular disorders. Chest 128, 585S-590S (2005).
126. Goumans, M. J., Lebrin, F. & Valdimarsdottir, G. Controlling the angiogenic switch: a balance between two distinct TGF-b receptor signaling pathways. Trends Cardiovasc. Med. 13, 301-307 (2003).
127. Ward, N. L. & Dumont, D. J. The angiopoietins and Tie2/Tek: adding to the complexity of cardiovascular development. Semin. Cell Dev. Biol. 13, 19-27 (2002).
128. Thurston, G. Role of angiopoietins and Tie receptor tyrosine kinases in angiogenesis and lymphangiogenesis. Cell Tissue Res. 314, 61-68 (2003).
129. Thurston, G. et al. The anti-inflammatory actions of angiopoietin-1. EXS 233-245 (2005).
130. Eklund, L. & Olsen, B. R. Tie receptors and their angiopoietin ligands are context-dependent regulators of vascular remodeling. Exp. Cell Res. 312, 630-641 (2006).
131. Fiedler, U. et al. Angiopoietin-2 sensitizes endothelial cells to TNF-α and has a crucial role in the induction of inflammation. Nature Med. 12, 235-239 (2006).
132. Arai, F. et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118, 149-161 (2004).
133. Tait, C. R. & Jones, P. F. Angiopoietins in tumours: the angiogenic switch. J. Pathol. 204, 1-10 (2004).
134. Kobayashi, H. & Lin, P. C. Angiopoietin/Tie2 signaling, tumor angiogenesis and inflammatory diseases. Front. Biosci. 10, 666-674 (2005).
135. Jones, N., Iljin, K., Dumont, D. J. & Alitalo, K. Tie receptors: new modulators of angiogenic and lymphangiogenic responses. Nature Rev. Mol. Cell Biol. 2, 257-267 (2001).
136. Saharinen, P. et al. Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2. J. Cell Biol. 169, 239-243 (2005).
137. Le Bras, B. et al. VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nature Neurosci. 9, 340-348 (2006).
138. Storkebaum, E. et al. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nature Neurosci. 8, 85-92 (2005). References 137 and 138 show that VEGF signalling is not confined to endothelial cells. VEGFC stimulates the proliferation of glial-cell precursors and VEGFA promotes the survival of motoneurons in an animal model of amyotrophic lateral sclerosis (ALS).
139. Li, D. Y. et al. Defective angiogenesis in mice lacking endoglin. Science 284, 1534-1537 (1999).
140. McAllister, K. A. et al. Endoglin, a TGF-β binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nature Genet. 8, 345-351 (1994).
141. Poschl, E. et al. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development 131, 1619-1628 (2004).
142. Matsui, K., Breitender-Geleff, S., Soleiman, A., Kowalski, H. & Kerjaschki, D. Podoplanin, a novel 43-kDa membrane protein, controls the shape of podocytes. Nephrol. Dial. Transplant. 14 (Suppl.1), 9-11 (1999).
143. Schacht, V. et al. T1α/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J. 22, 3546-3556 (2003).
144. Jackson, D. G. Biology of the lymphatic marker LYVE-1 and applications in research into lymphatic trafficking and lymphangiogenesis. APMIS 112, 526-538 (2004).
145. Hirakawa, S. et al. Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells. Am. J. Pathol. 162, 575-586 (2003).
146. Bamji, S. X. Cadherins: actin with the cytoskeleton to form synapses. Neuron 47, 175-178 (2005).
147. Tillet, E. et al. N-cadherin deficiency impairs pericyte recruitment, and not endothelial differentiation or sprouting, in embryonic stem cell-derived angiogenesis. Exp. Cell Res. 310, 392-400 (2005).
148. Tallquist, M. D., French, W. J. & Soriano, P. Additive effects of PDGF receptor β signaling pathways in vascular smooth muscle cell development. PLoS Biol. 1, e52 (2003).
149. Lindblom, P. et al. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev. 17, 1835-1840 (2003).