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Transcriptional Control of Lymphatic Endothelial Cell Type Specification

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Developmental Aspects of the Lymphatic Vascular System

Part of the book series: Advances in Anatomy, Embryology and Cell Biology ((ADVSANAT,volume 214))

Abstract

The lymphatic vasculature is the “sewer system” of our body as it plays an important role in transporting tissue fluids and extravasated plasma proteins back to the blood circulation and absorbs lipids from the intestinal tract. Malfunction of the lymphatic vasculature can result in lymphedema and obesity. The lymphatic system is also important for the immune response and is one of the main routes for the spreading of metastatic tumor cells. The development of the mammalian lymphatic vasculature is a stepwise process that requires the specification of lymphatic endothelial cell (LEC) progenitors in the embryonic veins, and the subsequent budding of those LEC progenitors from the embryonic veins to give rise to the primitive lymph sacs from which the entire lymphatic vasculature will eventually be derived. This process was first proposed by Florence Sabin over a century ago and was recently confirmed by several studies using lineage tracing and gene manipulation. Over the last decade, significant advances have been made in understanding the transcriptional control of lymphatic endothelial cell type differentiation. Here we summarize our current knowledge about the key transcription factors that are necessary to regulate several aspects of lymphatic endothelial specification and differentiation.

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References

  • Aranguren, X. L., Beerens, M., Coppiello, G., Wiese, C., Vandersmissen, I., Nigro, A. L., et al. (2013). COUP-TFII orchestrates venous and lymphatic endothelial identity by homo- or heterodimerisation with PROX1. Journal of Cell Science, 126(Pt 5), 1164–1175.

    Article  PubMed  CAS  Google Scholar 

  • Bos, F. L., Caunt, M., Peterson-Maduro, J., Planas-Paz, L., Kowalski, J., Karpanen, T., et al. (2011). CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo. Circulation Research, 109, 486–491.

    Article  PubMed  CAS  Google Scholar 

  • Brice, G., Mansour, S., Bell, R., Collin, J. R., Child, A. H., Brady, A. F., et al. (2002). Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24. Journal of Medical Genetics, 39, 478–483.

    Article  PubMed  CAS  Google Scholar 

  • Carter, T. C., & Phillips, J. S. (1954). RAGGED, a semidominant coat texture mutant in the house mouse. Journal of Heredity, 45, 151–154.

    Google Scholar 

  • Casley-Smith, J. R. (1980). The fine structure and functioning of tissue channels and lymphatics. Lymphology, 13, 177–183.

    PubMed  CAS  Google Scholar 

  • Cermenati, S., Moleri, S., Cimbro, S., Corti, P., Del Giacco, L., Amodeo, R., et al. (2008). Sox18 and Sox7 play redundant roles in vascular development. Blood, 111, 2657–2666.

    Article  PubMed  CAS  Google Scholar 

  • Chang, C. P., Neilson, J. R., Bayle, J. H., Gestwicki, J. E., Kuo, A., Stankunas, K., et al. (2004). A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis. Cell, 118, 649–663.

    Article  PubMed  CAS  Google Scholar 

  • Chen, C. Y., Bertozzi, C., Zou, Z., Yuan, L., Lee, J. S., Lu, M., et al. (2012). Blood flow reprograms lymphatic vessels to blood vessels. Journal of Clinical Investigation, 122, 2006–2017.

    Article  PubMed  CAS  Google Scholar 

  • Chen, L., Mupo, A., Huynh, T., Cioffi, S., Woods, M., Jin, C., et al. (2010). Tbx1 regulates Vegfr3 and is required for lymphatic vessel development. Journal of Cell Biology, 189, 417–424.

    Article  PubMed  CAS  Google Scholar 

  • Dagenais, S. L., Hartsough, R. L., Erickson, R. P., Witte, M. H., Butler, M. G., & Glover, T. W. (2004). Foxc2 is expressed in developing lymphatic vessels and other tissues associated with lymphedema-distichiasis syndrome. Gene Expression Patterns, 4, 611–619.

    Article  PubMed  CAS  Google Scholar 

  • Davis, R. B., Curtis, C. D., & Griffin, C. T. (2013). BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development. Development, 140, 1272–1281.

    Article  PubMed  CAS  Google Scholar 

  • de la Pompa, J. L., Timmerman, L. A., Takimoto, H., Yoshida, H., Elia, A. J., Samper, E., et al. (1998). Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature, 392, 182–186.

    Article  PubMed  Google Scholar 

  • De Val, S., & Black, B. L. (2009). Transcriptional control of endothelial cell development. Developmental Cell, 16, 180–195.

    Article  PubMed  Google Scholar 

  • Deng, Y., Atri, D., Eichmann, A., & Simons, M. (2013). Endothelial ERK signaling controls lymphatic fate specification. Journal of Clinical Investigation, 123, 1202–1215.

    Article  PubMed  CAS  Google Scholar 

  • Dumont, D. J., Jussila, L., Taipale, J., Lymboussaki, A., Mustonen, T., Pajusola, K., et al. (1998). Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science, 282, 946–949.

    Article  PubMed  CAS  Google Scholar 

  • Fang, J., Dagenais, S. L., Erickson, R. P., Arlt, M. F., Glynn, M. W., Gorski, J. L., et al. (2000). Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. American Journal of Human Genetics, 67, 1382–1388.

    Article  PubMed  CAS  Google Scholar 

  • Flister, M. J., Wilber, A., Hall, K. L., Iwata, C., Miyazono, K., Nisato, R. E., et al. (2009). Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1. Blood, 115, 418–429.

    Article  PubMed  Google Scholar 

  • Francois, M., Caprini, A., Hosking, B., Orsenigo, F., Wilhelm, D., Browne, C., et al. (2008). Sox18 induces development of the lymphatic vasculature in mice. Nature, 456, 643–647.

    Article  PubMed  CAS  Google Scholar 

  • Fritz-Six, K. L., Dunworth, W. P., Li, M., & Caron, K. M. (2008). Adrenomedullin signaling is necessary for murine lymphatic vascular development. Journal of Clinical Investigation, 118, 40–50.

    Article  PubMed  CAS  Google Scholar 

  • Gridley, T. (2010). Notch signaling in the vasculature. Developmental Biology, 92, 277–309.

    CAS  Google Scholar 

  • Hagerling, R., Pollmann, C., Andreas, M., Schmidt, C., Nurmi, H., Adams, R. H., et al. (2013). A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO Journal, 32(5), 629–644.

    Article  PubMed  Google Scholar 

  • Harada, K., Yamazaki, T., Iwata, C., Yoshimatsu, Y., Sase, H., Mishima, K., et al. (2009). Identification of targets of Prox1 during in vitro vascular differentiation from embryonic stem cells: Functional roles of HoxD8 in lymphangiogenesis. Journal of Cell Science, 122, 3923–3930.

    Article  PubMed  CAS  Google Scholar 

  • Harvey, N. L., Srinivasan, R. S., Dillard, M. E., Johnson, N. C., Witte, M. H., Boyd, K., et al. (2005). Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nature Genetics, 37, 1072–1081.

    Article  PubMed  CAS  Google Scholar 

  • Herpers, R., van de Kamp, E., Duckers, H. J., & Schulte-Merker, S. (2008). Redundant roles for Sox7 and Sox18 in arteriovenous specification in zebrafish. Circulation Research, 102, 12–15.

    Article  PubMed  CAS  Google Scholar 

  • Hogan, B. M., Bos, F. L., Bussmann, J., Witte, M., Chi, N. C., Duckers, H. J., & Schulte-Merker, S. (2009). Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nature Genetics, 41, 396–398.

    Article  PubMed  CAS  Google Scholar 

  • Hong, Y. K., Harvey, N., Noh, Y. H., Schacht, V., Hirakawa, S., Detmar, M., & Oliver, G. (2002). Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Developmental Dynamics, 225, 351–357.

    Article  PubMed  CAS  Google Scholar 

  • Hosking, B., Francois, M., Wilhelm, D., Orsenigo, F., Caprini, A., Svingen, T., et al. (2009). Sox7 and Sox17 are strain-specific modifiers of the lymphangiogenic defects caused by Sox18 dysfunction in mice. Development, 136, 2385–2391.

    Article  PubMed  CAS  Google Scholar 

  • Ichise, T., Yoshida, N., & Ichise, H. (2010). H-, N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in mice. Development, 137, 1003–1013.

    Article  PubMed  CAS  Google Scholar 

  • Irrthum, A., Devriendt, K., Chitayat, D., Matthijs, G., Glade, C., Steijlen, P. M., et al. (2003). Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. American Journal of Human Genetics, 72, 1470–1478.

    Article  PubMed  CAS  Google Scholar 

  • Johnson, N. C., Dillard, M. E., Baluk, P., McDonald, D. M., Harvey, N. L., Frase, S. L., & Oliver, G. (2008). Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes and Development, 22, 3282–3291.

    Article  PubMed  CAS  Google Scholar 

  • Kanady, J. D., Dellinger, M. T., Munger, S. J., Witte, M. H., & Simon, A. M. (2011). Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax. Developmental Biology, 354, 253–266.

    Article  PubMed  CAS  Google Scholar 

  • Kang, J., Yoo, J., Lee, S., Tang, W., Aguilar, B., Ramu, S., et al. (2010). An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells. Blood, 116, 140–150.

    Article  PubMed  CAS  Google Scholar 

  • Karkkainen, M. J., Haiko, P., Sainio, K., Partanen, J., Taipale, J., Petrova, T. V., et al. (2004). Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nature Immunology, 5, 74–80.

    Article  PubMed  CAS  Google Scholar 

  • Kazenwadel, J., Michael, M. Z., & Harvey, N. L. (2010). Prox1 expression is negatively regulated by miR-181 in endothelial cells. Blood, 116, 2395–2401.

    Article  PubMed  CAS  Google Scholar 

  • Kazenwadel, J., Secker, G. A., Liu, Y. J., Rosenfeld, J. A., Wildin, R. S., Cuellar-Rodriguez, J., et al. (2012). Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature. Blood, 119, 1283–1291.

    Article  PubMed  CAS  Google Scholar 

  • Khandekar, M., Brandt, W., Zhou, Y., Dagenais, S., Glover, T. W., Suzuki, N., et al. (2007). A Gata2 intronic enhancer confers its pan-endothelia-specific regulation. Development, 134, 1703–1712.

    Article  PubMed  CAS  Google Scholar 

  • Kokubo, H., Miyagawa-Tomita, S., Nakazawa, M., Saga, Y., & Johnson, R. L. (2005). Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system. Developmental Biology, 278, 301–309.

    Article  PubMed  CAS  Google Scholar 

  • Kriederman, B. M., MyLoyde, T. L., Witte, M. H., Dagenais, S. L., Witte, C. L., Rennels, M., et al. (2003). FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome. Human Molecular Genetics, 12, 1179–1185.

    Article  PubMed  CAS  Google Scholar 

  • Kulkarni, R. M., Greenberg, J. M., & Akeson, A. L. (2009). NFATc1 regulates lymphatic endothelial development. Mechanisms of Development, 126, 350–365.

    Article  PubMed  CAS  Google Scholar 

  • Lawson, N. D., Scheer, N., Pham, V. N., Kim, C. H., Chitnis, A. B., Campos-Ortega, J. A., et al. (2001). Notch signaling is required for arterial–venous differentiation during embryonic vascular development. Development, 128, 3675–3683.

    PubMed  CAS  Google Scholar 

  • Lee, S., Kang, J., Yoo, J., Ganesan, S. K., Cook, S. C., Aguilar, B., et al. (2009). Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate. Blood, 113, 1856–1859.

    Article  PubMed  CAS  Google Scholar 

  • Lim, K. C., Hosoya, T., Brandt, W., Ku, C. J., Hosoya-Ohmura, S., Camper, S. A., et al. (2012). Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning. Journal of Clinical Investigation, 122, 3705–3717.

    Article  PubMed  CAS  Google Scholar 

  • Lin, F. J., Chen, X., Qin, J., Hong, Y. K., Tsai, M. J., & Tsai, S. Y. (2010). Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development. Journal of Clinical Investigation, 120, 1694–1707.

    Article  PubMed  CAS  Google Scholar 

  • Mansir, T., Lacombe, D., Lamireau, T., Taine, L., Chateil, J. F., Le Bail, B., et al. (1999). Abdominal lymphatic dysplasia and 22q11 microdeletion. Genetic Counseling, 10, 67–70.

    PubMed  CAS  Google Scholar 

  • Mishima, K., Watabe, T., Saito, A., Yoshimatsu, Y., Imaizumi, N., Masui, S., et al. (2007). Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascades. Molecular Biology of the Cell, 18, 1421–1429.

    Article  PubMed  CAS  Google Scholar 

  • Murtomaki, A., Uh, M. K., Choi, Y. K., Kitajewski, C., Borisenko, V., Kitajewski, J., & Shawber, C. J. (2013). Notch1 functions as a negative regulator of lymphatic endothelial cell differentiation in the venous endothelium. Development, 140(11), 2365–2376.

    Article  PubMed  CAS  Google Scholar 

  • Niessen, K., Zhang, G., Ridgway, J. B., Chen, H., Kolumam, G., Siebel, C. W., & Yan, M. (2011). The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development. Blood, 118, 1989–1997.

    Article  PubMed  CAS  Google Scholar 

  • Norrmen, C., Ivanov, K. I., Cheng, J., Zangger, N., Delorenzi, M., Jaquet, M., et al. (2009). FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1. Journal of Cell Biology, 185, 439–457.

    Article  PubMed  CAS  Google Scholar 

  • Oliver, G. (2004). Lymphatic vasculature development. Nature Reviews Immunology, 4, 35–45.

    Article  PubMed  CAS  Google Scholar 

  • Oliver, G., Sosa-Pineda, B., Geisendorf, S., Spana, E. P., Doe, C. Q., & Gruss, P. (1993). Prox 1, a prospero-related homeobox gene expressed during mouse development. Mechanisms of Development, 44, 3–16.

    Article  PubMed  CAS  Google Scholar 

  • Ostergaard, P., Simpson, M. A., Connell, F. C., Steward, C. G., Brice, G., Woollard, W. J., et al. (2011). Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nature Genetics, 43, 929–931.

    Article  PubMed  CAS  Google Scholar 

  • Pan, M. R., Chang, T. M., Chang, H. C., Su, J. L., Wang, H. W., & Hung, W. C. (2009). Sumoylation of Prox1 controls its ability to induce VEGFR3 expression and lymphatic phenotypes in endothelial cells. Journal of Cell Science, 122, 3358–3364.

    Article  PubMed  CAS  Google Scholar 

  • Pedrioli, D. M., Karpanen, T., Dabouras, V., Jurisic, G., van de Hoek, G., Shin, J. W., et al. (2010). miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo. Molecular and Cellular Biology, 30, 3620–3634.

    Article  PubMed  CAS  Google Scholar 

  • Pendeville, H., Winandy, M., Manfroid, I., Nivelles, O., Motte, P., Pasque, V., et al. (2008). Zebrafish Sox7 and Sox18 function together to control arterial-venous identity. Developmental Biology, 317, 405–416.

    Article  PubMed  CAS  Google Scholar 

  • Pennisi, D., Bowles, J., Nagy, A., Muscat, G., & Koopman, P. (2000a). Mice null for sox18 are viable and display a mild coat defect. Molecular and Cellular Biology, 20, 9331–9336.

    Article  PubMed  CAS  Google Scholar 

  • Pennisi, D., Gardner, J., Chambers, D., Hosking, B., Peters, J., Muscat, G., et al. (2000b). Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice. Nature Genetics, 24, 434–437.

    Article  PubMed  CAS  Google Scholar 

  • Pereira, F. A., Qiu, Y., Tsai, M. J., & Tsai, S. Y. (1995). Chicken ovalbumin upstream promoter transcription factor (COUP-TF): expression during mouse embryogenesis. Journal of Steroid Biochemistry and Molecular Biology, 53, 503–508.

    Article  PubMed  CAS  Google Scholar 

  • Petrova, T. V., Karpanen, T., Norrmen, C., Mellor, R., Tamakoshi, T., Finegold, D., et al. (2004). Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nature Medicine, 10, 974–981.

    Article  PubMed  CAS  Google Scholar 

  • Petrova, T. V., Makinen, T., Makela, T. P., Saarela, J., Virtanen, I., Ferrell, R. E., et al. (2002). Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO Journal, 21, 4593–4599.

    Article  PubMed  CAS  Google Scholar 

  • Ranger, A. M., Grusby, M. J., Hodge, M. R., Gravallese, E. M., de la Brousse, F. C., Hoey, T., et al. (1998). The transcription factor NF-ATc is essential for cardiac valve formation. Nature, 392, 186–190.

    Article  PubMed  CAS  Google Scholar 

  • Roca, C., & Adams, R. H. (2007). Regulation of vascular morphogenesis by Notch signaling. Genes and Development, 21, 2511–2524.

    Article  PubMed  CAS  Google Scholar 

  • Sabin, F. (1902). On the origin of the lymphatics system from the veins and the development of the lymph hearts and the thoracic duct in the pig. The American Journal of Anatomy, 1, 367–389.

    Article  Google Scholar 

  • Sabine, A., Agalarov, Y., Maby-El Hajjami, H., Jaquet, M., Hagerling, R., Pollmann, C., et al. (2012). Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Developmental Cell, 22, 430–445.

    Article  PubMed  CAS  Google Scholar 

  • Sacchi, G., Weber, E., Agliano, M., Raffaelli, N., & Comparini, L. (1997). The structure of superficial lymphatics in the human thigh: Precollectors. Anatomical Record, 247, 53–62.

    Article  PubMed  CAS  Google Scholar 

  • Shan, S. F., Wang, L. F., Zhai, J. W., Qin, Y., Ouyang, H. F., Kong, Y. Y., et al. (2008). Modulation of transcriptional corepressor activity of prospero-related homeobox protein (Prox1) by SUMO modification. FEBS Letters, 582, 3723–3728.

    Article  PubMed  CAS  Google Scholar 

  • Shin, J. W., Min, M., Larrieu-Lahargue, F., Canron, X., Kunstfeld, R., Nguyen, L., et al. (2006). Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF) receptor-3 in lymphatic endothelium: A role for FGF signaling in lymphangiogenesis. Molecular Biology of the Cell, 17, 576–584.

    Article  PubMed  CAS  Google Scholar 

  • Slee, J. (1957a). The morphology and development of ‘ragged’— A mutant affecting the skin and hair of the house mouse I. Adult morphology. Journal of Genetics, 55, 100–121.

    Article  Google Scholar 

  • Slee, J. (1957b). The morphology and development of ragged—A mutant affecting the skin and hair of the house mouse II. Genetics, Embryology and Gross Juvenile Morphology. Journal of Genetics, 55, 570–584.

    Article  Google Scholar 

  • Srinivasan, R. S., Dillard, M. E., Lagutin, O. V., Lin, F. J., Tsai, S., Tsai, M. J., et al. (2007). Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature. Genes and Development, 21, 2422–2432.

    Article  PubMed  CAS  Google Scholar 

  • Srinivasan, R. S., Geng, X., Yang, Y., Wang, Y., Mukatira, S., Studer, M., et al. (2010). The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells. Genes and Development, 24, 696–707.

    Article  PubMed  CAS  Google Scholar 

  • Srinivasan, R. S., & Oliver, G. (2011). Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves. Genes and Development, 25, 2187–2197.

    Article  PubMed  CAS  Google Scholar 

  • Tsai, F. Y., Keller, G., Kuo, F. C., Weiss, M., Chen, J., Rosenblatt, M., et al. (1994). An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature, 371, 221–226.

    Article  PubMed  CAS  Google Scholar 

  • van der Putte, S. C. (1975). The early development of the lymphatic system in mouse embryos. Acta Morphologica Neerlando-Scandinavica, 13, 245–286.

    PubMed  Google Scholar 

  • Wigle, J. T., Harvey, N., Detmar, M., Lagutina, I., Grosveld, G., Gunn, M. D., et al. (2002). An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO Journal, 21, 1505–1513.

    Article  PubMed  CAS  Google Scholar 

  • Wigle, J. T., & Oliver, G. (1999). Prox1 function is required for the development of the murine lymphatic system. Cell, 98, 769–778.

    Article  PubMed  CAS  Google Scholar 

  • Xu, Y., Yuan, L., Mak, J., Pardanaud, L., Caunt, M., Kasman, I., et al. (2010). Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3. Journal of Cell Biology, 188, 115–130.

    Article  PubMed  CAS  Google Scholar 

  • Yagi, H., Furutani, Y., Hamada, H., Sasaki, T., Asakawa, S., Minoshima, S., et al. (2003). Role of TBX1 in human del22q11.2 syndrome. Lancet, 362, 1366–1373.

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki, T., Yoshimatsu, Y., Morishita, Y., Miyazono, K., & Watabe, T. (2009). COUP-TFII regulates the functions of Prox1 in lymphatic endothelial cells through direct interaction. Genes to Cells, 14, 425–434.

    Article  PubMed  CAS  Google Scholar 

  • Yang, Y., Garcia-Verdugo, J. M., Soriano-Navarro, M., Srinivasan, R. S., Scallan, J. P., Singh, M. K., et al. (2012). Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos. Blood, 120(11), 2340–2348.

    Article  PubMed  CAS  Google Scholar 

  • Yao, L. C., Baluk, P., Srinivasan, R. S., Oliver, G., & McDonald, D. M. (2012). Plasticity of button-like junctions in the endothelium of airway lymphatics in development and inflammation. American Journal of Pathology, 180, 2561–2575.

    Article  PubMed  CAS  Google Scholar 

  • Yoshimatsu, Y., Yamazaki, T., Mihira, H., Itoh, T., Suehiro, J., Yuki, K., et al. (2011). Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1. Journal of Cell Science, 124, 2753–2762.

    Article  PubMed  CAS  Google Scholar 

  • You, L. R., Lin, F. J., Lee, C. T., Demayo, F. J., Tsai, M. J., & Tsai, S. Y. (2005). Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature, 435, 98–104.

    Article  PubMed  CAS  Google Scholar 

  • Zheng, W., Tammela, T., Yamamoto, M., Anisimov, A., Holopainen, T., Kaijalainen, S., et al. (2011). Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor. Blood, 118, 1154–1162.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We want to thank Josh Stokes (St. Jude) for the generation of Fig. 2.1.

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Yang, Y., Oliver, G. (2014). Transcriptional Control of Lymphatic Endothelial Cell Type Specification. In: Kiefer, F., Schulte-Merker, S. (eds) Developmental Aspects of the Lymphatic Vascular System. Advances in Anatomy, Embryology and Cell Biology, vol 214. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1646-3_2

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