Pressing the right buttons: Signaling in lymphangiogenesis

Blood

Volumn 123, Issue 17, 2014, Pages 2614-2624

  Coso, Sanja ^a,b   Bovay, Esther ^a,b   Petrova, Tatiana V ^a,b,c  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^b UNIVERSITY OF LAUSANNE   (Switzerland)

^c EPFL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN RECEPTOR LIKE KINASE 1; ANGIOPOIETIN; BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 9; CALCIUM ION; CELL SURFACE RECEPTOR; COLLAGEN; ENDOGLIN; EPHRIN; JAGGED1; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE; NEUROPILIN 2; NOTCH RECEPTOR; NOTCH1 RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; RAF PROTEIN; RAS PROTEIN; SMAD2 PROTEIN; SMAD3 PROTEIN; TIE RECEPTOR; TRANSCRIPTION FACTOR NFAT; TRANSFORMING GROWTH FACTOR; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 2; VASCULOTROPIN C; VASCULOTROPIN D; VASCULOTROPIN RECEPTOR 3; VASCULOTROPIN A;

ANGIOGENESIS; ARTICLE; CALCIUM BINDING; CELL PROLIFERATION; HUMAN; INTRACELLULAR SIGNALING; LYMPH VESSEL; LYMPHANGIOGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; SIGNAL TRANSDUCTION; TISSUE PRESSURE; VASCULARIZATION; ANIMAL; GENE EXPRESSION REGULATION; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); PHYSIOLOGY; PROTEIN TERTIARY STRUCTURE; REVIEW;

ANGIOPOIETINS; ANIMALS; COLLAGEN; EPHRINS; GENE EXPRESSION REGULATION; HUMANS; LYMPHANGIOGENESIS; LYMPHATIC VESSELS; MITOGEN-ACTIVATED PROTEIN KINASES; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN STRUCTURE, TERTIARY; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3;

EID: 84902105359     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2013-12-297317     Document Type: Article

References (162)

1. Schulte-Merker S, Sabine A, Petrova TV. Lymphatic vascular morphogenesis in development, physiology, and disease. J Cell Biol. 2011;193(4):607-618.
2. Baluk P, Fuxe J, Hashizume H, et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med. 2007;204(10):2349- 2362. (Pubitemid 47529321)
3. Sabine A, Petrova T. V. Interplay of mechanotransduction, FOXC2, connexins, and calcineurin signaling in lymphatic valve formation. In: Kiefer F, Schulte-Merker S, eds. Developmental Aspects of the Lymphatic Vascular System, vol. 214. Springer, Vienna, Austrial; 2014:67-80.
4. Zawieja DC. Contractile physiology of lymphatics. Lymphat Res Biol. 2009;7(2):87-96.
5. Sabin FR. On the origin of the lymphatic system from the veins, and the development of the lymph hearts and thoracic duct in the pig. Am J Anat. 1902;1(3):367-389.
6. Huntington GS. The genetic interpretation of the development of the lymphatic system. Anat Rec. 1908;2(292):19-46.
7. Hägerling R, Pollmann C, Andreas M, et al. A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO J. 2013;32(5):629-644.
8. Yang Y, García-Verdugo JM, Soriano-Navarro M, et al. Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos. Blood. 2012;120(11): 2340-2348.
9. Wigle JT, Oliver G. Prox1 function is required for the development of the murine lymphatic system. Cell. 1999;98(6):769-778. (Pubitemid 29446894)
10. François M, Caprini A, Hosking B, et al. Sox18 induces development of the lymphatic vasculature in mice. Nature. 2008;456(7222): 643-647.
11. van Impel A, Zhao Z, Hermkens DMA, et al. Divergence of zebrafish and mouse lymphatic cell fate specification pathways. Development. 2014;141(6):1228-1238.
12. Srinivasan RS, Oliver G. Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves. Genes Dev. 2011;25(20): 2187-2197.
13. Yao L-C, Baluk P, Srinivasan RS, Oliver G, McDonald DM. Plasticity of button-like junctions in the endothelium of airway lymphatics in development and inflammation. Am J Pathol. 2012;180(6):2561-2575.
14. Betterman KL, Paquet-Fifield S, Asselin-Labat M-L, et al. Remodeling of the lymphatic vasculature during mouse mammary gland morphogenesis is mediated via epithelial-derived lymphangiogenic stimuli. Am J Pathol. 2012; 181(6):2225-2238.
15. Rutkowski JM, Ihm JE, Lee ST, et al. VEGFR-3 neutralization inhibits ovarian lymphangiogenesis, follicle maturation, and murine pregnancy. Am J Pathol. 2013;183(5): 1596-1607.
16. Petrova TV, Karpanen T, Norrmén C, et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med. 2004;10(9): 974-981. (Pubitemid 39273739)
17. Aebischer D, Iolyeva M, Halin C. The inflammatory response of lymphatic endothelium. Angiogenesis. 2013;doi:10.1007/ s10456-013-9404-3.
18. Kim H, Kataru RP, Koh GY. Regulation and implications of inflammatory lymphangiogenesis. Trends Immunol. 2012;33(7):350-356.
19. Huggenberger R, Ullmann S, Proulx ST, Pytowski B, Alitalo K, Detmar M. Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation. J Exp Med. 2010;207(10): 2255-2269.
20. Harvey NL, Gordon EJ. Deciphering the roles of macrophages in developmental and inflammation stimulated lymphangiogenesis. Vasc Cell. 2012;4(1):15.
21. Tan KW, Chong SZ, Wong FHS, et al. Neutrophils contribute to inflammatory lymphangiogenesis by increasing VEGF-A bioavailability and secreting VEGF-D. Blood. 2013;122(22):3666-3677.
22. Sleeman JP, Thiele W. Tumor metastasis and the lymphatic vasculature. Int J Cancer. 2009; 125(12):2747-2756.
23. Leong SPL, Nakakura EK, Pollock R, et al. Unique patterns of metastases in common and rare types of malignancy. J Surg Oncol. 2011; 103(6):607-614.
24. Mortimer P. Arm lymphoedema after breast cancer. Lancet Oncol. 2013;14(6):442-443.
25. Alitalo A, Detmar M. Interaction of tumor cells and lymphatic vessels in cancer progression. Oncogene. 2012;31(42):4499-4508.
26. Jain RK, Fenton BT. Intratumoral lymphatic vessels: a case of mistaken identity or malfunction? J Natl Cancer Inst. 2002;94(6): 417-421. (Pubitemid 34285090)
27. Kerjaschki D, Bago-Horvath Z, Rudas M, et al. Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse. J Clin Invest. 2011;121(5):2000-2012.
28. Kuroda K, Horiguchi A, Asano T, Asano T, Hayakawa M. Prediction of lymphatic invasion by peritumoral lymphatic vessel density in prostate biopsy cores. Prostate. 2008;68(10):1057-1063. (Pubitemid 351875177)
29. Karnezis T, Shayan R, Caesar C, et al. VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. Cancer Cell. 2012;21(2): 181-195.
30. He Y, Rajantie I, Ilmonen M, et al. Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis. Cancer Res. 2004;64(11):3737-3740. (Pubitemid 38697279)
31. Hirakawa S, Brown LF, Kodama S, Paavonen K, Alitalo K, Detmar M. VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood. 2007;109(3):1010-1017. (Pubitemid 46220646)
32. Feng Y, Wang W, Hu J, Ma J, Zhang Y, Zhang J. Expression of VEGF-C and VEGF-D as significant markers for assessment of lymphangiogenesis and lymph node metastasis in non-small cell lung cancer. Anat Rec (Hoboken). 2010;293(5):802-812.
33. Dadras SS, Lange-Asschenfeldt B, Velasco P, et al. Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes. Mod Pathol. 2005;18(9):1232-1242. (Pubitemid 43079923)
34. Das S, Sarrou E, Podgrabinska S, et al. Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses. J Exp Med. 2013;210(8): 1509-1528.
35. Harvey NL, Srinivasan RS, Dillard ME, et al. Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nat Genet. 2005;37(10):1072-1081. (Pubitemid 41486659)
36. Greene AK, Grant FD, Slavin SA. Lowerextremity lymphedema and elevated body-mass index. N Engl J Med. 2012;366(22):2136-2137.
37. Martel C, Li W, Fulp B, et al. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice. J Clin Invest. 2013; 123(4):1571-1579.
38. Lim HY, Thiam CH, Yeo KP, et al. Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BImediated transport of HDL. Cell Metab. 2013; 17(5):671-684.
39. Lim HY, Rutkowski JM, Helft J, et al. Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. Am J Pathol. 2009;175(3):1328- 1337.
40. Wiig H, Schröder A, Neuhofer W, et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest. 2013;123(7):2803-2815.
41. Machnik A, Neuhofer W, Jantsch J, et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009;15(5):545-552.
42. Impel A, Schulte-Merker S. A fisheye view on lymphangiogenesis. In: Kiefer F, Schulte-Merker S, eds. Developmental Aspects of the Lymphatic Vascular System, vol. 214. Springer, Vienna, Austria; 2014:153-165.
43. Alitalo K. The lymphatic vasculature in disease. Nat Med. 2011;17(11):1371-1380.
44. Karkkainen MJ, Haiko P, Sainio K, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol. 2004;5(1):74-80. (Pubitemid 38081471)
45. Küchler AM, Gjini E, Peterson-Maduro J, Cancilla B, Wolburg H, Schulte-Merker S. Development of the zebrafish lymphatic system requires VEGFC signaling. Curr Biol. 2006; 16(12):1244-1248. (Pubitemid 43867297)
46. Jeltsch M, Leppänen V-M, Saharinen P, Alitalo K. Receptor tyrosine kinase-mediated angiogenesis. Cold Spring Harb Perspect Biol. 2013;5(9):1-22.
47. Joukov V, Sorsa T, Kumar V, et al. Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J. 1997;16(13): 3898-3911. (Pubitemid 27281006)
48. Dumont DJ, Jussila L, Taipale J, et al. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science. 1998; 282(5390):946-949. (Pubitemid 28507528)
49. Karkkainen MJ, Ferrell RE, Lawrence EC, et al. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet. 2000;25(2):153-159. (Pubitemid 30394984)
50. Karkkainen MJ, Saaristo A, Jussila L, et al. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci USA. 2001; 98(22):12677-12682. (Pubitemid 33020005)
51. Gordon K, Schulte D, Brice G, et al. Mutation in vascular endothelial growth factor-C, a ligand for vascular endothelial growth factor receptor-3, is associated with autosomal dominant milroy-like primary lymphedema. Circ Res. 2013;112(6): 956-960.
52. Villefranc JA, Nicoli S, Bentley K, et al. A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development. Development. 2013;140(7):1497-1506.
53. Planas-Paz L, Strilić B, Goedecke A, Breier G, Fässler R, Lammert E. Mechanoinduction of lymph vessel expansion. EMBO J. 2012;31(4): 788-804.
54. Yuan L, Moyon D, Pardanaud L, et al. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development. 2002;129(20): 4797-4806. (Pubitemid 35282411)
55. Xu Y, Yuan L, Mak J, et al. Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3. J Cell Biol. 2010;188(1):115-130.
56. Lin F-J, Chen X, Qin J, Hong Y-K, Tsai M-J, Tsai SY. Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development. J Clin Invest. 2010;120(5):1694-1707.
57. Coma S, Allard-Ratick M, Akino T, van Meeteren LA, Mammoto A, Klagsbrun M. GATA2 and Lmo2 control angiogenesis and lymphangiogenesis via direct transcriptional regulation of neuropilin-2. Angiogenesis. 2013; 16(4):939-952.
58. Caunt M, Mak J, Liang WC, et al. Blocking neuropilin-2 function inhibits tumor cell metastasis. Cancer Cell. 2008;13(4):331-342. (Pubitemid 351446192)
59. Murakami M, Zheng Y, Hirashima M, et al. VEGFR1 tyrosine kinase signaling promotes lymphangiogenesis as well as angiogenesis indirectly via macrophage recruitment. Arterioscler Thromb Vasc Biol. 2008;28(4): 658-664. (Pubitemid 351651323)
60. Dellinger MT, Meadows SM, Wynne K, Cleaver O, Brekken RA. Vascular endothelial growth factor receptor-2 promotes the development of the lymphatic vasculature. PLoS ONE. 2013; 8(9):e74686.
61. Wirzenius M, Tammela T, Uutela M, et al. Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. J Exp Med. 2007;204(6):1431-1440. (Pubitemid 46919880)
62. Nilsson I, Bahram F, Li X, et al. VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts. EMBO J. 2010; 29(8):1377-1388.
63. Alders M, Hogan BM, Gjini E, et al. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nat Genet. 2009;41(12): 1272-1274.
64. Van Balkom IDC, Alders M, Allanson J, et al. Lymphedema-lymphangiectasia- mental retardation (Hennekam) syndrome: a review. Am J Med Genet. 2002;112(4):412-421.
65. Hogan BM, Bos FL, Bussmann J, et al. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat Genet. 2009;41(4): 396-398.
66. Bos FL, Caunt M, Peterson-Maduro J, et al. CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo. Circ Res. 2011;109(5): 486-491.
67. Le Guen L, Karpanen T, Schulte D, et al. Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis. Development. 2014;141(6):1239-1249.
68. Jeltsch M, Jha SK, Tvorogov D, et al. CCBE1 enhances lymphangiogenesis via ADAMTS3-mediated VEGF-C activation. Circulation. Epub: February 19, 2014; doi:10.1161/CIRCULATIONAHA.113.002779.
69. Zou Z, Enis DR, Bui H, et al. The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythropoiesis. Blood. 2013;121(16): 3228-3236.
70. Weijts BGMW, van Impel A, Schulte-Merker S, de Bruin A. Atypical E2fs control lymphangiogenesis through transcriptional regulation of Ccbe1 and Flt4. PLoS ONE. 2013; 8(9):e73693.
71. Eilken HM, Adams RH. Dynamics of endothelial cell behavior in sprouting angiogenesis. Curr Opin Cell Biol. 2010;22(5):617-625.
72. Mäkinen T, Adams RH, Bailey J, et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev. 2005;19(3):397-410. (Pubitemid 40189302)
73. Katsuta H, Fukushima Y, Maruyama K, et al. EphrinB2-EphB4 signals regulate formation and maintenance of funnel-shaped valves in corneal lymphatic capillaries. Invest Ophthalmol Vis Sci. 2013;54(6):4102-4108.
74. Wang Y, Nakayama M, Pitulescu ME, et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature. 2010; 465(7297):483-486.
75. Sawamiphak S, Seidel S, Essmann CL, et al. Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature. 2010;465(7297):487- 491.
76. Nakayama A, Nakayama M, Turner CJ, Höing S, Lepore JJ, Adams RH. Ephrin-B2 controls PDGFRβ internalization and signaling. Genes Dev. 2013;27(23):2576-2589.
77. Abéngozar MA, de Frutos S, Ferreiro S, et al. Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth. Blood. 2012;119(19):4565-4576.
78. Eklund L, Saharinen P. Angiopoietin signaling in the vasculature. Exp Cell Res. 2013;319(9): 1271-1280.
79. Jeansson M, Gawlik A, Anderson G, et al. Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest. 2011;121(6):2278-2289.
80. Qu X, Tompkins K, Batts LE, Puri M, Baldwin S. Abnormal embryonic lymphatic vessel development in Tie1 hypomorphic mice. Development. 2010;137(8):1285-1295.
81. D'Amico G, Korhonen EA, Waltari M, Saharinen P, Laakkonen P, Alitalo K. Loss of endothelial Tie1 receptor impairs lymphatic vessel development-brief report. Arterioscler Thromb Vasc Biol. 2010;30(2):207-209.
82. Gale NW, Thurston G, Hackett SF, et al. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell. 2002;3(3):411-423.
83. Dellinger M, Hunter R, Bernas M, et al. Defective remodeling and maturation of the lymphatic vasculature in Angiopoietin-2 deficient mice. Dev Biol. 2008;319(2):309-320.
84. Fagiani E, Lorentz P, Kopfstein L, Christofori G. Angiopoietin-1 and 22 exert antagonistic functions in tumor angiogenesis, yet both induce lymphangiogenesis. Cancer Res. 2011;71(17): 5717-5727.
85. Tammela T, Saaristo A, Lohela M, et al. Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Blood. 2005;105(12): 4642-4648. (Pubitemid 40807283)
86. Koh GY. Orchestral actions of angiopoietin-1 in vascular regeneration. Trends Mol Med. 2013; 19(1):31-39.
87. Gerald D, Chintharlapalli S, Augustin HG, Benjamin LE. Angiopoietin-2: an attractive target for improved antiangiogenic tumor therapy. Cancer Res. 2013;73(6):1649-1657.
88. Roca C, Adams RH. Regulation of vascular morphogenesis by Notch signaling. Genes Dev. 2007;21(20):2511-2524. (Pubitemid 47607663)
89. Phng LK, Gerhardt H. Angiogenesis: a team effort coordinated by notch. Dev Cell. 2009; 16(2):196-208.
90. Shawber CJ, Funahashi Y, Francisco E, et al. Notch alters VEGF responsiveness in human and murine endothelial cells by direct regulation of VEGFR-3 expression. J Clin Invest. 2007; 117(11):3369-3382. (Pubitemid 350096993)
91. Niessen K, Zhang G, Ridgway JB, et al. The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development. Blood. 2011; 118(7):1989-1997.
92. Zheng W, Tammela T, Yamamoto M, et al. Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor. Blood. 2011;118(4):1154-1162.
93. Geudens I, Herpers R, Hermans K, et al. Role of delta-like-4/Notch in the formation and wiring of the lymphatic network in zebrafish. Arterioscler Thromb Vasc Biol. 2010;30(9):1695-1702.
94. Kang J, Yoo J, Lee S, et al. An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells. Blood. 2010;116(1):140-150.
95. Murtomaki A, Uh MK, Choi YK, et al. Notch1 functions as a negative regulator of lymphatic endothelial cell differentiation in the venous endothelium. Development. 2013;140(11): 2365-2376.
96. Jakobsson L, van Meeteren LA. Transforming growth factor β family members in regulation of vascular function: in the light of vascular conditional knockouts. Exp Cell Res. 2013; 319(9):1264-1270.
97. ten Dijke P, Arthur HM. Extracellular control of TGFbeta signalling in vascular development and disease. Nat Rev Mol Cell Biol. 2007;8(11): 857-869. (Pubitemid 47622560)
98. Park SO, Lee YJ, Seki T, et al. ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2. Blood. 2008;111(2): 633-642.
99. Moya IM, Umans L, Maas E, et al. Stalk cell phenotype depends on integration of Notch and Smad1/5 signaling cascades. Dev Cell. 2012; 22(3):501-514.
100. Larrivée B, Prahst C, Gordon E, et al. ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway. Dev Cell. 2012;22(3): 489-500.
101. Nguyen HLLY, Lee YJ, Shin J, et al. TGF-β signaling in endothelial cells, but not neuroepithelial cells, is essential for cerebral vascular development. Lab Invest. 2011;91(11): 1554-1563.
102. David L, Mallet C, Keramidas M, et al. Bone morphogenetic protein-9 is a circulating vascular quiescence factor. Circ Res. 2008;102(8): 914-922. (Pubitemid 351591550)
103. Carvalho RL, Itoh F, Goumans MJ, et al. Compensatory signalling induced in the yolk sac vasculature by deletion of TGFbeta receptors in mice. J Cell Sci. 2007;120(Pt 24):4269-4277.
104. Armulik A, Genové G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21(2):193-215.
105. Langlois D, Hneino M, Bouazza L, et al. Conditional inactivation of TGF-β type II receptor in smooth muscle cells and epicardium causes lethal aortic and cardiac defects. Transgenic Res. 2010;19(6):1069-1082.
106. Niessen K, Zhang G, Ridgway JB, Chen H, Yan M. ALK1 signaling regulates early postnatal lymphatic vessel development. Blood. 2010; 115(8):1654-1661.
107. Oka M, Iwata C, Suzuki HI, et al. Inhibition of endogenous TGF-β signaling enhances lymphangiogenesis. Blood. 2008;111(9): 4571-4579.
108. James JM, Nalbandian A, Mukouyama YS. TGFβ signaling is required for sprouting lymphangiogenesis during lymphatic network development in the skin. Development. 2013; 140(18):3903-3914.
109. Levet S, Ciais D, Merdzhanova G, et al. Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation. Blood. 2013;122(4):598-607.
110. Yoshimatsu Y, Lee YG, Akatsu Y, et al. Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression. Proc Natl Acad Sci USA. 2013;110(47): 18940-18945.
111. Dunworth WP, Cardona-Costa J, Bozkulak EC, et al. Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos. Circ Res. 2014;114(1):56-66.
112. Avraham T, Daluvoy S, Zampell J, et al. Blockade of transforming growth factor-b1 accelerates lymphatic regeneration during wound repair. Am J Pathol. 2010;177(6): 3202-3214.
113. Vittet D, Merdzhanova G, Prandini M-H, Feige J-J, Bailly S. TGFb1 inhibits lymphatic endothelial cell differentiation from mouse embryonic stem cells. J Cell Physiol. 2012; 227(11):3593-3602.
114. Tammela T, Zarkada G, Nurmi H, et al. VEGFR- 3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling. Nat Cell Biol. 2011;13(10):1202-1213.
115. Zhang L, Zhou F, Han W, et al. VEGFR-3 ligandbinding and kinase activity are required for lymphangiogenesis but not for angiogenesis. Cell Res. 2010;20(12):1319-1331.
116. Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995;376(6535):62-66.
117. Ricard N, Ciais D, Levet S, et al. BMP9 and BMP10 are critical for postnatal retinal vascular remodeling. Blood. 2012;119(25):6162-6171.
118. Sridurongrit S, Larsson J, Schwartz R, Ruiz- Lozano P, Kaartinen V. Signaling via the Tgf-β type I receptor Alk5 in heart development. Dev Biol. 2008;322(1):208-218.
119. Jiao K, Langworthy M, Batts L, Brown CB, Moses HL, Baldwin HS. Tgfbeta signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development. Development. 2006;133(22): 4585-4593. (Pubitemid 46017832)
120. Hellström M, Phng L-K, Hofmann JJ, et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 2007; 445(7129):776-780. (Pubitemid 46279716)
121. Sato TN, Tozawa Y, Deutsch U, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature. 1995; 376(6535):70-74.
122. Ichise T, Yoshida N, Ichise HH. H-, N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in mice. Development. 2010; 137(6):1003-1013.
123. Henkemeyer M, Rossi DJ, Holmyard DP, et al. Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein. Nature. 1995;377(6551):695-701.
124. Lapinski PE, Kwon S, Lubeck BA, et al. RASA1 maintains the lymphatic vasculature in a quiescent functional state in mice. J Clin Invest. 2012;122(2):733-747.
125. Mouta-Bellum C, Kirov A, Miceli-Libby L, et al. Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85α, p55α, and p50α. Dev Dyn. 2009;238(10):2670-2679.
126. Zhou F, Chang Z, Zhang L, et al. Akt/Protein kinase B is required for lymphatic network formation, remodeling, and valve development. Am J Pathol. 2010;177(4):2124-2133.
127. Zeini M, Hang CT, Lehrer-Graiwer J, Dao T, Zhou B, Chang C-P. Spatial and temporal regulation of coronary vessel formation by calcineurin-NFAT signaling. Development. 2009; 136(19):3335-3345.
128. Sabine A, Agalarov Y, Maby-El Hajjami H, et al. Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Dev Cell. 2012;22(2):430-445.
129. Castellano E, Downward J. Role of RAS in the regulation of PI 3-kinase. In: Rommel C, Vanhaesebroeck B, Vogt PK, eds. Phosphoinositide 3-Kinase in Health and Disease, vol. 346. Springer, Berlin, Germany; 2011:143-169.
130. Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22(2):153-183. (Pubitemid 32458157)
131. Schubbert S, Zenker M, Rowe SL, et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet. 2006;38(3):331-336.
132. Lo IFM, Brewer C, Shannon N, et al. Severe neonatal manifestations of Costello syndrome. J Med Genet. 2008;45(3):167-171. (Pubitemid 351373746)
133. Kerr B, Delrue MA, Sigaudy S, et al. Genotypephenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases. J Med Genet. 2006;43(5):401-405.
134. Boon LM, Mulliken JB, Vikkula M. RASA1: variable phenotype with capillary and arteriovenous malformations. Curr Opin Genet Dev. 2005;15(3):265-269. (Pubitemid 40726049)
135. de Wijn RS, Oduber CE, Breugem CC, Alders M, Hennekam RC, van der Horst CM. Phenotypic variability in a family with capillary malformations caused by a mutation in the RASA1 gene. Eur J Med Genet. 2012;55(3):191-195.
136. Burrows PE, Gonzalez-Garay ML, Rasmussen JC, et al. Lymphatic abnormalities are associated with RASA1 gene mutations in mouse and man. Proc Natl Acad Sci USA. 2013; 110(21):8621-8626.
137. Xu K, Sacharidou A, Fu S, et al. Blood vessel tubulogenesis requires Rasip1 regulation of GTPase signaling. Dev Cell. 2011;20(4): 526-539.
138. Ren B, Deng Y, Mukhopadhyay A, et al. ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish. J Clin Invest. 2010;120(4): 1217-1228.
139. Hong CC, Peterson QP, Hong J-Y, Peterson RT. Artery/vein specification is governed by opposing phosphatidylinositol-3 kinase and MAP kinase/ERK signaling. Curr Biol. 2006;16(13): 1366-1372. (Pubitemid 43975369)
140. Deng Y, Atri D, Eichmann A, Simons M. Endothelial ERK signaling controls lymphatic fate specification. J Clin Invest. 2013;123(3): 1202-1215.
141. Vanhaesebroeck B, Stephens L, Hawkins P. PI3K signalling: the path to discovery and understanding. Nat Rev Mol Cell Biol. 2012; 13(3):195-203.
142. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9(8):550-562.
143. Castellano E, Downward J. RAS interaction with PI3K. Genes Cancer. 2011;2(3):261-274.
144. Graupera M, Potente M. Regulation of angiogenesis by PI3K signaling networks. Exp Cell Res. 2013;319(9):1348-1355.
145. Mäkinen T, Veikkola T, Mustjoki S, et al. Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J. 2001;20(17): 4762-4773. (Pubitemid 32848629)
146. Coso S, Zeng Y, Opeskin K, Williams ED. Vascular endothelial growth factor receptor-3 directly interacts with phosphatidylinositol 3-kinase to regulate lymphangiogenesis. PLoS ONE. 2012;7(6):e39558.
147. Garmy-Susini B, Avraamides CJ, Desgrosellier JS, et al. PI3Kα activates integrin α4b1 to establish a metastatic niche in lymph nodes. Proc Natl Acad Sci USA. 2013;110(22): 9042-9047.
148. Fruman DA, Snapper SB, Yballe CM, et al. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85α. Science. 1999;283(5400):393-397.
149. Gupta S, Ramjaun AR, Haiko P, et al. Binding of ras to phosphoinositide 3-kinase p110α is required for ras-driven tumorigenesis in mice. Cell. 2007;129(5):957-968. (Pubitemid 46802703)
150. Kurek KC, Luks VL, Ayturk UM, et al. Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet. 2012; 90(6):1108-1115.
151. Hoey SEH, Eastwood D, Monsell F, Kangesu L, Harper JI, Sebire NJ. Histopathological features of Proteus syndrome. Clin Exp Dermatol. 2008; 33(3):234-238. (Pubitemid 351550616)
152. Johnson EN, Lee YM, Sander TL, et al. NFATc1 mediates vascular endothelial growth factor-induced proliferation of human pulmonary valve endothelial cells. J Biol Chem. 2003;278(3): 1686-1692. (Pubitemid 36801401)
153. Zaichuk TA, Shroff EH, Emmanuel R, Filleur S, Nelius T, Volpert OV. Nuclear factor of activated T cells balances angiogenesis activation and inhibition. J Exp Med. 2004;199(11):1513-1522. (Pubitemid 38780406)
154. Schweighofer B, Testori J, Sturtzel C, et al. The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation. Thromb Haemost. 2009;102(3):544-554.
155. Minami T, Jiang S, Schadler K, et al. The calcineurin-NFAT-angiopoietin-2 signaling axis in lung endothelium is critical for the establishment of lung metastases. Cell Rep. 2013;4(4):709-723.
156. Norrmén C, Ivanov KI, Cheng J, et al. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1. J Cell Biol. 2009;185(3):439-457.
157. Kulkarni RM, Greenberg JM, Akeson AL. NFATc1 regulates lymphatic endothelial development. Mech Dev. 2009;126(5-6):350-365.
158. Fish JE, Cybulsky MI. Taming endothelial activation with a microRNA. J Clin Invest. 2012; 122(6):1967-1970.
159. Hartmann D, Thum T. MicroRNAs and vascular (dys)function. Vascul Pharmacol. 2011;55(4): 92-105.
160. Boon RA. MicroRNAs control vascular endothelial growth factor signaling. Circ Res. 2012;111(11):1388-1390.
161. Kazenwadel J, Michael MZ, Harvey NL. Prox1 expression is negatively regulated by miR-181 in endothelial cells. Blood. 2010;116(13): 2395-2401.
162. Pedrioli DM, Karpanen T, Dabouras V, et al. miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo. Mol Cell Biol. 2010;30(14):3620-3634.