[en] OBJECTIVE: To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development.
METHODS AND RESULTS:
In zebrafish embryos, sprouts from the axial vein have lymphangiogenic potential because they give rise to the first lymphatics. Knockdown of delta-like-4 (Dll4) or its receptors Notch-1b or Notch-6 in zebrafish impaired lymphangiogenesis. Dll4/Notch silencing reduced the number of sprouts producing the string of parchordal lymphangioblasts; instead, sprouts connecting to the intersomitic vessels were formed. At a later phase, Notch silencing impaired navigation of lymphatic intersomitic vessels along their arterial templates.
CONCLUSIONS:
These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Geudens, I.
Herpers, R.
Hermans, K.
Segura, I.
Ruiz de Almodovar, Carine
Bussmann, J.
De Smet, F.
Vandevelde, W.
Hogan, B. M.
Siekmann, A.
Claes, F.
Moore, J. C.
Pistocchi, A. S.
Loges, S.
Mazzone, M.
Mariggi, G.
Bruyère, F.
Cotelli, F.
Kerjaschki, D.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Tammela T, Alitalo K. Lymphangiogenesis: molecular mechanisms and future promise. Cell. 2010;140:460-476.
Francois M, Koopman P, Beltrame M. SoxF genes: key players in the development of the cardio-vascular system. Int J Biochem Cell Biol. 2010;42:445-448.
Gale NW, Thurston G, Hackett SF, Renard R, Wang Q, McClain J, Martin C, Witte C, Witte MH, Jackson D, Suri C, Campochiaro PA, Wiegand SJ, Yancopoulos GD. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell. 2002;3:411-423.
De Smet F, Segura I, De Bock K, Hohensinner PJ, Carmeliet P. Mechanisms of vessel branching: filopodia on endothelial tip cells lead the way. Arterioscler Thromb Vasc Biol. 2009;29:639-649.
Tammela T, Saaristo A, Lohela M, Morisada T, Tornberg J, Norrmen C, Oike Y, Pajusola K, Thurston G, Suda T, Yla-Herttuala S, Alitalo K. Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Blood. 2005;105:4642-4648.
Hogan BM, Bos FL, Bussmann J, Witte M, Chi NC, Duckers HJ, Schulte-Merker S. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat Genet. 2009;41:396-398.
Lawson ND, Scheer N, Pham VN, Kim CH, Chitnis AB, Campos-Ortega JA, Weinstein BM. Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development. 2001; 128:3675-3683.
Herbert SP, Huisken J, Kim TN, Feldman ME, Houseman BT, Wang RA, Shokat KM, Stainier DY. Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation. Science. 2009;326:294-298.
Swift MR, Weinstein BM. Arterial-venous specification during development. Circ Res. 2009;104:576-588.
Shawber CJ, Kitajewski J. Arterial regulators taken up by lymphatics. Lymphat Res Biol. 2008;6:139-143.
Emuss V, Lagos D, Pizzey A, Gratrix F, Henderson SR, Boshoff C. KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia. PLoS Pathog. 2009;5:e1000616.
Lawson ND, Weinstein BM. In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol. 2002;248:307-318.
Parsons MJ, Pisharath H, Yusuff S, Moore JC, Siekmann AF, Lawson N, Leach SD. Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas. Mech Dev. 2009;126:898-912.
Chittenden TW, Claes F, Lanahan AA, Autiero M, Palac RT, Tkachenko EV, Elfenbein A, Ruiz De Almodovar C, Dedkov E, Tomanek R, Li W, Westmore M, Singh JP, Horowitz A, Mulligan-Kehoe MJ, Moodie KL, Zhuang ZW, Carmeliet P, Simons M. Selective regulation of arterial branching morphogenesis by synectin. Dev Cell. 2006;10:783-795.
Yaniv K, Isogai S, Castranova D, Dye L, Hitomi J, Weinstein BM. Live imaging of lymphatic development in the zebrafish. Nat Med. 2006;12:711-716.
Kuchler 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;16:1244-1248.
Ota H, Katsube KI, Ogawa JI, Yanagishita M. Hypoxia/Notch signaling in primary culture of rat lymphatic endothelial cells. FEBS Lett. 2007; 581:5220-5226.
Geling A, Steiner H, Willem M, Bally-Cuif L, Haass C. A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Rep. 2002;3:688-694.
Hogan BM, Herpers R, Witte M, Helotera H, Alitalo K, Duckers HJ, Schulte-Merker S. Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries. Development. 2009;136:4001-4009.
Lin FJ, Chen X, Qin J, Hong YK, Tsai MJ, Tsai YT. Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development. J Clin Invest. 2010;120:1694-1707.
Leslie JD, Ariza-McNaughton L, Bermange AL, McAdow R, Johnson SL, Lewis J. Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis. Development. 2007;134:839-844.
Siekmann AF, Lawson ND. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature. 2007;445:781-784.
O'Neill CF, Urs S, Cinelli C, Lincoln A, Nadeau RJ, Leon R, Toher J, Mouta-Bellum C, Friesel RE, Liaw L. Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth. Am J Pathol. 2007; 171:1023-1036.
Kang J, Yoo J, Lee S, Tang W, Aguilar B, Ramu S, Choi I, Otu HH, Shin JW, Dotto GP, Koh CJ, Detmar M, Hong YK. An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells. Blood. 2010;116:140-150.
Srinivasan RS, Geng X, Yang Y, Wang Y, Mukatira S, Studer M, Porto MPR, Lagutin O, Oliver G. The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells. Genes Dev. 2010;24:696-707.
Bak M, Fraser SE. Axon fasciculation and differences in midline kinetics between pioneer and follower axons within commissural fascicles. Development. 2003;130:4999-5008.
Makita T, Sucov HM, Gariepy CE, Yanagisawa M, Ginty DD. Endo-thelins are vascular-derived axonal guidance cues for developing sympathetic neurons. Nature. 2008;452:759-763.
Bussmann J, Bos LF, Urasaki A, Kawakami K, Duckers HJ, Schulte-Merker S. Arteries provide essential guidance cues for lymphatic endo-thelial cells in the zebrafish trunk. Development. 2010; Epub ahead of print July 7.