Frye M, Taddei A, Dierkes C, Martinez-Corral I, Fielden M, Ortsäter H, Kazenwadel J, Calado DP, Ostergaard P, Salminen M, He L, Harvey N, Kiefer F, Mäkinen T. Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program. Nat Commun 9:1511 (2018) doi: 10.1038/s41467-018-03959-6. (Article)

Zhang Y, Ulvmar MH, Stanczuk L, Martinez-Corral I, Frye M, Alitalo, K, Mäkinen T. Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms. Nat Commun 9:1296 (2018) doi: 10.1038/s41467-018-03692-0. (PubMed)

Zhang Y, Daubel N, Stritt S, Makinen T. Transient loss of venous integrity during developmental vascular remodeling leads to red blood cell extravasation and clearance by lymphatic vessels. Development 145: pii: dev156745 (2018) doi: 10.1242/dev.156745. (PubMed)


Wang Y, Jin Y, Mäe MA, Zhang Y, Ortsäter H, Betsholtz C, Mäkinen T#, Jakobsson L#. Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity. Development. 144:3590-3601 (2017). (PubMed)

Lyons O, Saha P, Seet C, Kuchta A, Arnold A, Grover S, Rashbrook V, Sabine A, Vizcay-Barrena G, Patel A, Ludwinski F, Padayachee S, Kume T, Kwak BR, Brice G, Mansour S, Ostergaard P, Mortimer P, Jeffery S, Brown N, Makinen T, Petrova TV, Modarai B, Smith A. Human venous valve disease caused by mutations in FOXC2 and GJC2. J Exp Med 214:2437-2452 (2017). (PubMed)

Pujol F, Hodgson T, Martinez-Corral I, Prats AC, Devenport D, Takeichi M, Genot E, Mäkinen T, Francis-West P, Garmy-Susini B, Tatin F. Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization During Lymphatic Valve Morphogenesis. Arterioscler Thromb Vasc Biol. 37:1732-1735 (2017) (PubMed)

Potente M, Makinen T. Vascular heterogeneity and specialization in development and disease. Nat Rev Mol Cell Biol. 18:477-494 (2017). Review. (PubMed)

Vaahtomeri K, Karaman S, Mäkinen T, Alitalo K. Lymphangiogenesis guidance by paracrine and pericellular factors. Genes Dev. 31:1615-1634 (2017). Review. (PubMed)



Ulvmar MH, Makinen T. Heterogeneity in the lymphatic vascular system and its origin. Cardiovasc Res 111:310-21 (2016). Review. (PubMed)

Martin-Almedina S*, Martinez-Corral I*, Holdhus R, Vicente A, Fotiou E, Lin S, Kjell Petersen K, Simpson MA, Höischen A, Gilissen C, Jeffery H, Atton G, Brice G, Gordon K, Wiseman JW, Wedin M, Rockson SG, Jeffery S, Mortimer PS, Snyder MP, Berland S, Mansour S, Makinen T, Ostergaard P. Kinase inactivating mutations in EPHB4 cause autosomal dominant lymphatic-related hydrops fetalis. J Clin Invest. 26:3080-8 (2016). (PubMed)

Martinez-Corral I, Stanczuk L, Frye M, Ulvmar MH, Dieguez-Hurtado R, Olmeda D, Makinen T, Ortega S. Vegfr3-CreERT2 mouse, a new genetic tool for targeting the lymphatic system. Angiogenesis. 19:433-45 (2016). (PubMed)

Ulvmar MH, Martinez-Corral I, Stanczuk L, Mäkinen T. Pdgfrb-Cre targets lymphatic endothelial cells of both venous and non-venous origins. Genesis. 54:350-8 (2016). (PubMed)

Aspelund A, Robociuc MR, Karaman S, Makinen T, Alitalo K. Lymphatic system in cardiovascular medicine. Circulation Res 118:515-30 (2016). Review. (PubMed)



Zarkada G, Heinolainen K, Makinen T, Kubota Y, Alitalo K. VEGFR3 does not sustain retinal angiogenesis without VEGFR2. Proc Natl Acad Sci USA 112:761-766 (2015).

Stanczuk L, Martinez-Corral I, Ulvmar MH, Zhang Y, Lavina B, Fruttiger M, Adams RH, Saur D, Betsholtz C, Ortega S, Alitalo K, Graupera M, Mäkinen T. cKit lineage hemogenic endothelium-derived cells contribute to mesenteric lymphatic vessels. Cell Rep 10:1708-1721 (2015).

Martinez-Corral I, Ulvmar MH, Stanczuk L, Tatin F, Kizhatil K, John SWM, Alitalo K, Ortega S, Makinen T. Non-venous origin of dermal lymphatic vasculature. Circ Res 116:1649-1654 (2015). Cover story with an Editorial. (PubMed)

Rouhani S, Eccles J, Riccardi P, Peske J, Tewalt E, Cohen J, Liblau R, Mäkinen T, Engelhard V. Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction. Nat Commun 10:6771 (2015).

Bianchi R, Teijeira A, Proulx ST, Christiansen AJ, Seidel CD, Rulicke T, Mäkinen T, Hägerling R, Halin C, Detmar M. A transgenic Prox1-Cre-tdTomato reporter mouse for lymphatic vessel research. PLoS ONE 10:e0122976 (2015).

Sabine A, Bovay E, Demir CS, Kimura W, Jaquet M, Agalarov Y, Zangger N, Scallan JP, Graber W, Gulpinar E, Kwak BR, Mäkinen T, Martinez-Corral I, Ortega S, Delorenzi M, Kiefer F, Davis MJ, Djonov V, Miura N, Petrova TV. FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature. J Clin Invest 125:3861-77 (2015).



Hess PR, Rawnsley DR, Jakus Z, Yang Y, Sweet DT, Fu J, Herzog B, Lu M, Nieswandt B, Oliver G, Makinen T, Xia L, Kahn ML. Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life. J Clin Invest 124:273-84 (2014).

Aspelund A, Tammela T, Antila S, Nurmi H, Leppanen VM, Zarkada G, Stanczuk L, Francois M, Makinen T, Saharinen P, Immonen I, Alitalo K. The Schlemm’s canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel. J Clin Invest 124:3975-3986 (2014).

Park DY, Lee J, Park I, Choi D, Lee S, Song S, Hwang Y, Hong KY, Nakaoka Y, Makinen T, Kim P, Alitalo K, Hong YK, Koh GY. Lymphatic regulator PROX1 determines Schlemm’s canal integrity and identity. J Clin Invest 124:3960-3974 (2014).



Nikitenko LL, Shimosawa T, Henderson S, Mäkinen T, Shimosawa H, Qureshi U, Pedley B, Rees MCP, Fujita T and Boshoff C. Adrenomedullin haploinsufficiency predisposes to secondary lymphedema. J Invest Dermat 133:1768-76 (2013).

Tatin F, Taddei A, Weston A, Fuchs E, Devenport D, Tissir F, Makinen T. Planar cell polarity protein Celsr1 regulates endothelial adherens junctions and directed cell rearrangements during lymphatic valve morphogenesis. Dev Cell 15:31-44 (2013). Cover story with a Preview. Evaluated ‘Recommended’ in Faculty of 1000 Biology. (PubMed)



Ostergaard P, Simpson MA, Mendola A, Vasudevan P, Connell FC, van Impel A, Moore AT, Loeys BL, Ghalamkarpour A, Onoufriadis A, Martinez-Corral I, Devery S, Leroy JG, van Laer L, Singer A, Bialer MG, McEntagart M, Quarrell O, Brice G, Trembath RC, Schulte-Merker S, Makinen T, Vikkula M, Mortimer PS, Mansour S, Jeffery S. Mutations in KIF11 cause autosomal dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am J Hum Gen 90:356-62 (2012).

Sabine A, Agalarov Y, Maby-El Hajjami H, Jaquet M, Hägerling R, Pollmann C, Bebber D, Pfenniger A, Miura N, Dormond O, Calmes JM, Adams RH, Mäkinen T, Kiefer F, Kwak BR, Petrova TV. PROX1, FOXC2, and mechanotransduction cooperate to control Connexin37 and Calcineurin during lymphatic-valve formation. Dev Cell 22:430-45 (2012).

Wallgard E, Nitzsche A, Larsson J, Guo X, Dietrich LC, Dimberg A, Olofsson T, Ponten FC, Mäkinen T, Kalen M, Hellström M. Paladin (X99384) is expressed in the vasculature and shifts from endothelial to vascular smooth muscle cells during mouse development. Dev Dyn 241:770-86 (2012).

Chen CY, Bertozzi C, Zou Z, Yuan L, Lee JS, Lu M, Stachelek SJ, Srinivasa S, Guo L, Vicente A, Mericko P, Levy RJ, Makinen T, Oliver G, Kahn ML. Blood flow reprograms lymphatic vessels to blood vessels. J Clin Invest 122:2006-17 (2012).

Lutter S, Xie S, Tatin F, Makinen T. Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation. J Cell Biol 197:837-49 (2012). Evaluated ‘Must read’ in Faculty of 1000 Biology. (


Mellor RH, Tate N, Stanton AWB, Hubert CE, Mäkinen T, Smith A, Burnand KG, Jeffery S, Levick JR, Mortimer, PS. Mutations in FOXC2 in humans (lymphoedema distichiasis syndrome) cause lymphatic dysfunction on dependency. J Vasc Res 48:397–407 (2011).

Calvo CF, Fontaine RH, Soueid J, Tammela T, Makinen T, Alfaro-Cervello C, Bonnaud F, Miguez A, Benhaim L, Xu Y, Barallobre MJ, Moutkine I, Lyytikkä J, Tatlisumak T, Pytowski B, Zalc B, Richardson W, Kessaris N, Garcia-Verdugo JM, Alitalo K, Eichmann A, Thomas JL. Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis. Genes Dev 25:831-844 (2011).


Bazigou E, Lyons OTA, Smith A, Venn GE, Cope C, Brown NA, Makinen T. Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice. J Clin Invest 121:2984-92 (2011). Cover story. Evaluated ‘Exceptional’ in Faculty of 1000 Biology. (PubMed)

Ostergaard P, Simpson MA, Connell FC, Steward C, Brice G, Woollard WJ, Kilo T, Smithson S, Lunt P, Murday VA, Hodgson S, Keenan R, Pilz D, Martinez-Corral I, Makinen T, Mortimer P, Jeffery S, Trembath RC, Mansour S. Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat Gen 43:929-31 (2011).

Tammela T, Zarkada G, Nurmi H, Jakobsson L, Heinolainen K, Tvorogov D, Zheng W, Franco CA, Murtomäki A, Aranda E, Miura N, Ylä-Herttuala S, Fruttiger M, Mäkinen T, Eichmann A, Pollard JW, Gerhardt H, Alitalo K. VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signaling. Nat Cell Biol 13:1202-13 (2011).



Foster KE, Gordon J, Cardenas K, Veiga-Fernandes H, Makinen T, Grigova E, Wilkinson DG, Blackburn CC, Richie E, Manley NR, Adams RH, Kioussis D, Coles MC. EphB-ephrin-B2 interactions are required for thymus migration during organogenesis. Proc Natl Acad Sci USA 107:13414-13419 (2010).

Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy Al, Deutsch U, Luthi U, Barberis A, Benjamin LE, Mäkinen T, Nobes CD, Adams RH. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 465:483-486 (2010).

Mellor RH, Huberts CE, Stanton AWB, Tate N, Smith A, Burnand KG, Jeffery S, Makinen T, Levick JR, Mortimer PS. Lymphatic dysfunction, not aplasia, underlies Milroy disease. Microcirculation 17:281-296 (2010).



Bazigou E, Xie S, Chen C, Weston A, Miura N, Sorokin L, Adams R, Muro A, Sheppard D, Makinen T. Integrin-a9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis. Dev Cell 17:175-186 (2009). Featured article. Evaluated ‘Recommended’ in Faculty of 1000 Biology. (PubMed)

selected articles - 2008

Karpanen T, Wirzenius M, Mäkinen T, Veikkola T, Haisma HJ, Achen, MG, Stacker SA, Pytowski B, Ylä-Herttuala S, Alitalo K. Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation. Am J Pathol 169:708-718 (2006).

Mäkinen T, Adams RH, Bailey J, Lu Q, Ziemiecki A, Alitalo K, Klein R, Wilkinson GA. PDZ interaction site in ephrinB2 is required for the remodelling of lymphatic vasculature. Genes Dev 19:397-410 (2005). Cover story.

Dixelius J, Mäkinen T, Wirzenius M, Karkkainen MJ, Wernstedt C, Alitalo K, Claesson-Welsh L. Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites. J Biol Chem 278:40973-40979 (2003).

Petrova TV*, Mäkinen T*, Mäkelä TP, Saarela J, Virtanen I, Ferrell RE, Finegold DG, Kerjaschki D, Ylä-Herttuala S, Alitalo K. Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J 21:4593-4599 (2002). * = equal contribution

Mäkinen T, Veikkola T, Mustjoki S, Karpanen T, Catimel B, Nice EC, Wise L, Mercer A, Kowalski H, Kerjaschki D, Stacker SA, Achen MG, Alitalo K. Isolated lymphatic endothelial cells transduce growth, survival and migration signals via the VEGF-C/D receptor VEGFR-3. EMBO J 20:4762-4773 (2001).

Veikkola T, Jussila L, Makinen T, Karpanen T, Jeltsch M, Petrova TV, Kubo H, Thurston G, McDonald DM, Jackson DG, Achen MG, Stacker SA, Alitalo K. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J 20:1223-1231 (2001).

Mäkinen T, Jussila L, Veikkola T, Karpanen T, Kettunen MI, Pulkkanen KJ, Kauppinen R, Jackson DG, Kubo H, Nishikawa SI, Ylä-Herttuala S, Alitalo K. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med 2:199-205 (2001). Cover story with ‘News and Views’.