CellBio  Vol.2 No.4 , December 2013
The Ortholog of LYVE-1 Is Required for Thoracic Duct Formation in Zebrafish
Abstract: LYVE-1 (also termed CRSBP-1), a 120-kDa disulfide-linked dimeric type I membrane glycoprotein, is a specific marker for lymphatic endothelial cells (LECs) and exhibits multiple ligand (hyaluronic acid and growth factors/cytokines) binding activity in mammals. Recent studies indicate that LYVE-1/CRSBP-1 ligands (VEGF-A165, PDGF-BB, oligopeptides containing the cell-surface retention sequence (CRS) motifs of VEGF-A165 and PDGF-BB) induce opening of lymphatic intercellular junctions in vitro and in vivo. To determine the function of the ortholog of mammalian LYVE-1 in zebrafish, we cloned it (zLyve-1). The cloned cDNA (zLyve1) encodes a 328-amino-acid type I membrane glycoprotein. The protein and genomic structure evidence supports the notion that the cloned zLyve-1 is the ortholog of LYVE-1 in zebrafish. zLyve-1 expressed in cultured cells by transfection exhibits hyaluronic acid binding activity but lacks the growth factor binding activity seen in mammalian homologs. Knockdown of zLyve-1 levels by embryo microinjection with a specific antisense morpholino oligonucleotide (MO2) in wild-type and Tg(fli1:EGFP)-transgenic zebrafish causes defects in thoracic duct (TD) formation. Such zebrafish injected with MO2 also exhibit impaired TD flow (as determined by intramuscular injection of FITC-dextran). The phenotypes in these zebrafish injected with MO2 are reversed by co-injection with zLyve1cDNA. In situ hybridization reveals that zLyve-1 is expressed in the posterior cardinal vein (PCV). Expression of zLyve-1 at the highest level in the PCV occurs at 3 dpf which coincides with the time for TD formation in zebrafish development. These results suggest that zLyve-1 is required for TD formation. They also suggest that zLyve-1 is distinct from mammalian LYVE-1 in its role in lymphatic function.
Cite this paper: Chen, W. , Tseng, W. , Lin, G. , Schreiner, A. , Chen, H. , M. Voigt, M. , Yuh, C. , Wu, J. , Huang, S. and Huang, J. (2013) The Ortholog of LYVE-1 Is Required for Thoracic Duct Formation in Zebrafish. CellBio, 2, 228-247. doi: 10.4236/cellbio.2013.24026.

[1]   C. Boensch, M. D. Kuo, D. T. Connolly, S. S. Huang and J. S. Huang, “Identification, Purificationand Characterization of Cell-Surface Retention Sequence-Binding Proteins from Human SK-Hep Cells and Bovine Liver Plasma Membranes,” Journal of Biological Chemistry, Vol. 270, No. 4, 1995, pp. 1807-1816.

[2]   C. Boensch, S. S. Huang, D. T. Connolly and J. S. Huang, “Cell Surface Retention Sequence Binding Protein-1 Interacts with the V-Sis Gene Product and Platelet-Derived Growth Factor Beta-Type Receptor in Simian Sarcoma Virus-Transformed Cells,” Journal of Biological Chemistry, Vol. 274, 1999, pp. 10582-10589.

[3]   S. S. Huang, F.-M. Tan, Y.-H. Huang, S.-C. Hsu, S.-T. Chen and J. S. Huang, “Cloning, Expression, Characterization, and Role in Autocrine Cell Growth of Cell Surface Retention Sequence Binding Protein-1,” Journal of Biological Chemistry, Vol. 278, No. 44, 2003, pp. 43855-43869.

[4]   S. Banerji, J. Ni, S. X. Wang, S. Clasper, J. Su, R. Tammi, M. Jones and D. G. Jackson, “LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-Specific Receptor for Hyaluronan,” Journal of Cell Biology, Vol. 144, No. 4, 1999, pp. 789-801.

[5]   R. Prevo, S. Banerji, D. J. Ferguson, S. Clasper and D. G. Jackson, “Mouse LYVE-1 Is an Endocytic Receptor for Hyaluronan in Lymphatic Endothelium,” Journal of Biological Chemistry, Vol. 276, No. 37, 2001, pp. 19420-19430.

[6]   S. S. Huang, I.-H. Liu, T. Smith, M. R. Shah, F. E. Johnson and J. S. Huang, “CRSBP-1/LYVE-1-Null Mice Exhibited Identifiable Morphological and Functional Alterations of Lymphatic Capillary Vessels,” FEBS Letters, Vol. 580, No. 26, 2006, pp. 6259-6268.

[7]   W.-H. Hou, I.-H. Liu, C. C. Tsai, F. E. Johnson, S. S. Huang and J. S. Huang, “CRSBP-1/LYVE-1 Ligands Induce Disruption of Lymphatic Intercellular Adhesion by Inducing Tyrosinephosphorylation and Internalization of VE-Cadherin,” Journal of Cell Science, Vol. 124, 2011, pp. 1231-1244.

[8]   W.-H. Hou, I.-H. Liu, S. S. Huang and J. S. Huang, “CRSBP-1/LYVE-1 Ligands Stimulate Contraction of the CRSBP-1-Associated ER Network in Lymphatic Endothelial Cells,” FEBS Letters, Vol. 586, No. 10, 2012, pp. 1480-1487.

[9]   A. M. Kuchler, E. Gjini, J. Peterson-Maduro, B. Cancilla, H. Wolburg and S. Schulte-Merker, “Development of the Zebrafish Lymphatic System Requires VEGF-C Signaling,” Current Biology, Vol. 16, No. 12, 2006, pp. 1244-1248.

[10]   K. Yaniv, S. Isogai, D. Castranova, L. Dye, J. Hitomi and B. M. Weinstein, “Live Imaging of Lymphatic Development in the Zebrafish,” Nature Medicine, Vol. 12, No. 6, 2006, pp. 711-716.

[11]   B. M. Hogan, L. Frank, F. L. Bos, J. Bussman, M. Witte, N. C. Chi, H. J. Duckers and S. Schulte-Merker, “Ccbe1 Is Required for Embryonic Lymphangiogenesis and Venous Sprouting,” Nature Genetics, Vol. 41, No. 4, 2009, pp. 396-398.

[12]   B. M. Hogan, R. Herpers, M. Witte, H. Helotera, K. Alitalo, H. J. Duckers and S. Schulte-Merker, “Vegfc/Flt4 Signalling Is Suppressed by Dll4 in Developing Zebrafish Intersegmental Arteries,” Development, Vol. 136, No. 4, 2009, pp. 4001-4009.

[13]   J. S. Eisen and J. C. Smith, “Controlling Morpholino Experiments: Don’t Stop Making Antisense,” Development, Vol. 135, No. 10, 2001, pp. 1735-1743.

[14]   S. Isogai, J. Hitomi, K. Yaniv and B. M. Weinstein, “Zebrafish as a New Animal Model to Study Lymphangiogenesis,” Anatomical Science International, Vol. 84, No. 3, 2009, pp. 102-111.

[15]   M. C. McKinney and B. M. Weinstein, “Chapter 4. Using the Zebrafish to Study Vessel Formation,” Methods in Enzymology, Vol. 444, 2008, pp. 65-97.

[16]   M. V. Flores, C. J. Hall, K. E. Crosier and P. S. Crosier, “Visualization of Embryonic Lymphangiogenesis Advances the Use of the Zebrafish Model for Research in Cancer and Lymphatic Pathologies,” Developmental Dynamics, Vol. 239, No. 7, 2010, pp. 2128-2135.

[17]   A. J. Day and G. D. Prestwich, “Hyaluronan-Binding Proteins: Tying Up the Giant,” Journal of Biological Chemistry, Vol. 277, No. 7, 2002, pp. 4585-4588.

[18]   N. Platonova, G. Miquel, B. Regenfuss, S. Taouji, C. Cursiefen, E. Chevet and A. Bikfalvi, “Evidence for the Interaction of Fibroblast Growth Factor-2 with the Lymphaticendothelial Cell Marker LYVE-1,” Blood, Vol. 121, No. 7, 2013, pp. 1229-1237.

[19]   L. Del Giacco, A. Pistocchi and A. Ghilardi, “Prox1b Activity Is Essential in Zebrafish Lymphangiogenesis,” PLoS One, Vol. 5, No. 10, 2010, p. e13170.

[20]   A. M. Küchler, E. Gjini, J. Peterson-Maduro, B. Cancilla, H. Wolburg and S. Schulte-Merker, “Development of the Zebrafish Lymphatic System Requires VEGFC Signaling,” Current Biology, Vol. 16, No. 12, 2006, pp. 1244-1248.

[21]   S. Tao, M. Witte, R. J. Bryson-Richardson, P. D. Currie, B. M. Hogan and S. Schulte-Merker, “Zebrafish Prox1b Mutants Develop a Lymphatic Vasculature, and Prox1b Does Not Specifically Mark Lymphatic Endothelial Cells,” PLoS One, Vol. 6, No. 12, 2011, p. e28934.

[22]   C. E. Eckfeldt, E. M. Mendenhall, C. M. Flynn, T. F. Wang, M. A. Pickart, S. M. Grindle, S. C. Ekker and C. M. Verfaillie, “Functional Analysis of Human Hematopoietic Stem Cell Gene Expression Using Zebrafish,” PLoS Biology, Vol. 3, No. 8, 2005, p. e254.

[23]   D. Sheng, D. Qu, K. H. Kwok, S. S. Ng, A. Y. Lim, S. S. Aw, C. W. Lee, W. K. Sung, E. K. Tan, T. Lufkin, S. Jesuthasan, M. Sinnakaruppan and J. Liu, “Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect,” PLoS Genetics, Vol. 6, No. 4, 2010, p. e1000914.

[24]   S.-J. Lee, T.-H. Chan, T.-C. Chen, B.-K. Liao, P.-P. Hwang and H. Lee, “LPA1 Is Essential for Lymphatic Vessel Development in Zebrafish,” FASEB Journal, Vol. 22, No. 19, 2008, pp. 3706-3715.

[25]   J. Bussmann, F. L. Bos, A. Urasaki, K. Kawakami, H. J. Duckers and S. Schulte-Merker, “Arteries Provide Essential Guidance Cues for Lymphatic Endothelial Cells in the Zebrafish Trunk,” Development, Vol. 137, No. 16, 2010, pp. 2653-2657.

[26]   N. W. Gale, R. Prevo, J. Espinosa, D. J. Ferguson, M. G. Dominguez, G. D. Yancopoulos, G. Thurston and D. G. Jackson, “Normal Lymphatic Development and Function in Mice Deficient for the Lymphatic Hyaluronan Receptor LYVE-1,” Molecular and Cellular Biology, Vol. 27, No. 2, 2007, pp. 595-604.

[27]   M. X. Luong, J. Tam, Q. Lin, J. Hagendoorn, K. J. Moore, T. P. Padera, B. Seed, D. Fukumura, R. Kucherlapati and R. K. Jain, “Lack of Lymphatic Vessel Phenotype in LYVE-1/CD44 Double Knockout Mice,” Journal of Cellular Physiology, Vol. 219, No. 2, 2009, pp. 430-437.

[28]   D. F. Robbiani, R. A. Finch, D. Jager, W. A. Muller, A. C. Sartorelli and G. J. Randolph, “The Leukotriene C(4) Transporter MRP1 Regulates CCL19 (MIP-3β, ELC)-Dependent Ilization of Dendritic Cells to Lymph Nodes,” Cell, Vol. 103, No. 5, 2000, pp. 757-768.

[29]   L. Tort, J. C. Balasch and S. Mackenzie, “Fish Immune System. A Crossroads between Innate and Adaptive Responses,” Inmunologia, Vol. 22, No. 3, 2003, pp. 277- 286.