[en] In amniotes, the pancreatic mesenchyme plays a crucial role in pancreatic epithelium growth, notably through the secretion of fibroblast growth factors. However, the factors involved in the formation of the pancreatic mesenchyme are still largely unknown. In this study, we characterize, in zebrafish embryos, the pancreatic lateral plate mesoderm, which is located adjacent to the ventral pancreatic bud and is essential for its specification and growth. We firstly show that the endoderm, by expressing the fgf24 gene at early stages, triggers the patterning of the pancreatic lateral plate mesoderm. Based on the expression of isl1, fgf10 and meis genes, this tissue is analogous to the murine pancreatic mesenchyme. Secondly, Fgf10 acts redundantly with Fgf24 in the pancreatic lateral plate mesoderm and they are both required to specify the ventral pancreas. Our results unveil sequential signaling between the endoderm and mesoderm that is critical for the specification and growth of the ventral pancreas, and explain why the zebrafish ventral pancreatic bud generates the whole exocrine tissue.
Ahlgren, U., Jonsson, J. and Edlund, H. (1996). The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice. Development 122, 1409-1416.
Ahlgren, U., Pfaff, S. L., Jessell, T. M., Edlund, T. and Edlund, H. (1997). Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 385, 257-260.
Alexander, J., Rothenberg, M., Henry, G. L. and Stainier, D. Y. (1999). casanova plays an early and essential role in endoderm formation in zebrafish. Dev. Biol. 215, 343-357.
Apelqvist, A., Ahlgren, U. and Edlund, H. (1997). Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas. Curr. Biol. 7, 801-804.
Bhushan, A., Itoh, N., Kato, S., Thiery, J. P., Czernichow, P., Bellusci, S. and Scharfmann, R. (2001). Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development 128, 5109-5117.
Biemar, F., Argenton, F., Schmidtke, R., Epperlein, S., Peers, B. and Driever, W. (2001). Pancreas development in zebrafish: early dispersed appearance of endocrine hormone expressing cells and their convergence to form the definitive islet. Dev. Biol. 230, 189-203.
dilorio, P., Alexa, K., Choe, S. K., Etheridge, L. and Sagerstrom, C. G. (2007). TALE-family homeodomain proteins regulate endodermal sonic hedgehog expression and pattern the anterior endoderm. Dev Biol. 304, 221-231.
Dong, P. D., Munson, C. A., Norton, W., Crosnier, C., Pan, X., Gong, Z., Neumann, C. J. and Stainier, D. Y. (2007). Fgf10 regulates hepatopancreatic ductal system patterning and differentiation. Nat. Genet. 39, 397-402.
Draper, B. W., Stock, D. W. and Kimmel, C. B. (2003). Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development. Development 130, 4639-4654.
Field, H. A., Dong, P. D., Bels, D. and Stainier, D. Y. (2003). Formation of the digestive system in zebrafish. II. Pancreas morphogenesis. Dev. Biol. 261, 197-208.
Fischer, S., Draper, B. W. and Neumann, C. J. (2003). The zebrafish fgf24 mutant identifies an additional level of Fgf signaling involved in vertebrate forelimb initiation. Development 130, 3515-3524.
Gittes, G. K., Galante, P. E., Hanahan, D., Rutter, W. J. and Debase, H. T. (1996). Lineage-specific morphogenesis in the developing pancreas: role of mesenchymal factors. Development 122, 439-447.
Golosow, N. and Grobstein, C. (1962). Epitheliomesenchymal interaction in pancreatic morphogenesis. Dev. Biol. 4, 242-255.
Hauptmann, G. and Gerster, T. (1994). Two-color whole-mount in situ hybridization to vertebrate and Drosophila embryos. Trends Genet. 10, 266.
Hebrok, M., Kim, S. K. and Melton, D. A. (1998). Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev. 12, 1705-1713.
Horne-Badovinac, S., Rebagliati, M. and Stainier, D. Y. (2003). A cellular framework for gut-looping morphogenesis in zebrafish. Science 302, 662-665.
Itoh, N. and Ornitz, D. M. (2004). Evolution of the Fgf and Fgfr gene families. Trends Genet 20, 563-569.
Jacquemin, P., Lemaigre, F. P. and Rousseau, G. G. (2003). The Onecut transcription factor HNF-6 (CC-1) is required for timely specification of the pancreas and acts upstream of Pdx-1 in the specification cascade. Dev. Biol. 258, 105-116.
Jacquemin, P., Yoshitomi, H., Kashima, Y., Rousseau, G. G., Lemaigre, F. P. and Zaret, K. S. (2006). An endothelial-mesenchymal relay pathway regulates early phases of pancreas development. Dev. Biol. 290, 189-199.
Jonsson, J., Carlsson, L., Edlund, T. and Edlund, H. (1994). Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 371, 606-609.
Katoh, Y. and Katoh, M. (2005). Comparative genomics on FGF7, FGF10, FGF22 orthologs, and identification of fgf25. Int. J. Mol. Med. 16, 767-770.
Kawaguchi, Y., Cooper, B., Gannon, M., Ray, M., MacDonald, R. J. and Wright C. V. (2002). The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat. Genet. 32, 128-134.
Kim, S. K., Hebrok, M. and Melton, D. A. (1997). Notochord to endoderm signaling is required for pancreas development. Development 124, 4243-4252.
Kimmel, C. B., Ballard, W. W., Kimmel, S. R., Ullmann, B. and Schilling, T. F. (1995). Stages of embryonic development of the zebrafish. Dev. Dyn. 203, 253-310.
Korzh, S., Emelyanov, A. and Korzh, V. (2001). Developmental analysis of ceruloplasmin gene and liver formation in zebrafish. Mech. Dev. 103, 137-139.
Korzh, V., Edlund, T. and Thor, S. (1993). Zebrafish primary neurons initiate expression of the LIM homeodomain protein lsl-1 at the end of gastrulation. Development 118, 417-425.
Korzh, V., Sleptsova, I., Liao, J., He, J. and Gong, Z. (1998). Expression of zebrafish bHLH genes ngn1 and nrd defines distinct stages of neural differentiation. Dev. Dyn. 213, 92-104.
Kumar, M. and Melton, D.(2003). Pancreas specification: a budding question. Curr. Opin. Genet. Dev. 13, 401-407.
Kumar, M., Jordan, N., Melton, D. and Grapin-Botton, A. (2003). Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate. Dev. Biol. 259, 109-122.
Lammert, E., Cleaver, O. and Melton, D. (2003). Role of endothelial cells in early pancreas and liver development. Mech. Dev. 120, 59-64.
Li, H., Arber, S., Jessell, T. M. and Edlund, H. (1999). Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nat. Genet. 23, 67-70.
Li, Z., Manna, P., Kobayashi, H., Spilde, T., Bhatia, A., Preuett, B., Prasadan, K., Hembree, M. and Gittes, G. K. (2004). Multifaceted pancreatic mesenchymal control of epithelial lineage selection. Dev. Biol. 269, 252-263.
Lin, J. W., Biankin, A. V., Horb, M. E., Ghosh, B., Prasad, N. B., Yee, N. S., Pack, M. A. and Leach, S. D. (2004). Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas. Dev. Biol. 270, 474-486.
Mavropoulos, A., Devos, N., Biemar, F., Zecchin, E., Argenton, F., Edlund, H., Motte, P., Martial, J. A. and Peers, B. (2005). sox4b is a key player of pancreatic alpha cell differentiation in zebrafish. Dev. Biol. 285, 211-223.
Milewski, W. M., Duguay, S. J., Chan, S. J. and Steiner, D. F. (1998). Conservation of PDX-1 structure, function, and expression in zebrafish. Endocrinology 139, 1440-1449.
Miralles, F., Czernichow, P., Ozaki, K., Koh, N. and Scharfmann, R. (1999). Signaling through fibroblast growth factor receptor 2b plays a key role in the development of the exocrine pancreas. Proc. Natl. Acad. Sci. USA 96, 6267-6272.
Mohammadi, M., McMahon, G., Sun, L., Tang, C., Hirth, P., Yeh, B. K., Hubbard, S. R. and Schlessinger, J. (1997). Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 276, 955-960.
Norton, W. H., Ledin, J., Grandel, H. and Neumann, C. J. (2005). HSPG synthesis by zebrafish Ext2 and Extl3 is required for Fgf10 signalling during limb development. Development 132, 4963-4973.
Ober, E. A., Verkade, H., Field, H. A. and Stainier, D. Y. (2006). Mesodermal Wnt2b signalling positively regulates liver specification. Nature 442, 688-691.
Odenthal, J. and Nusslein-Volhard, C. (1998). fork head domain genes in zebrafish. Dev. Genes Evol. 208, 245-258.
Oulad-Abdelghani, M., Chazaud, C., Bouillet, P., Sapin, V., Chambon, P. and Dolle, P. (1997). Meis2, a novel mouse Pbx-related homeobox gene induced by retinoic acid during differentiation of P19 embryonal carcinoma cells. Dev. Dyn. 210, 173-183.
Pictet, R. L., Clark, W. R., Williams, R. H. and Rutter, W. J. (1972). An ultrastructural analysis of the developing embryonic pancreas. Dev. Biol. 29, 436-467.
Roy, S., Qiao, T., Wolff, C. and Ingham, P. W. (2001). Hedgehog signaling pathway is essential for pancreas specification in the zebrafish embryo. Curr. Biol. 11, 1358-1363.
Sagerstrom, C. G., Kao, B. A., Lane, M. E. and Sive, H. (2001). Isolation and characterization of posteriorly restricted genes in the zebrafish gastrula. Dev. Dyn. 220, 402-408.
Spooner, B. S., Walther, B. T. and Rutter, W. J. (1970). The development of the dorsal and ventral mammalian pancreas in vivo and in vitro. J. Cell Biol. 47, 235-246.
Wan, H., Korzh, S., Li, Z., Mudumana, S. P., Korzh, V., Jiang, Y. J., Lin, S. and Gong, Z. (2006). Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter. Exp. Cell Res. 312, 1526-1539.
Wendik, B., Maier, E. and Meyer, D. (2004). Zebrafish mnx genes in endocrine and exocrine pancreas formation. Dev. Biol. 268, 372-383.
Westerfield, M. (11995). The Zebrafish Book: Guide for the Laboratory Use of Zebrafish (Danio Rerio). Eugene, OR: University of Oregon Press.
Ye, F., Duvillie, B. and Scharfmann, R. (2005). Fibroblast growth factors 7 and 10 are expressed in the human embryonic pancreatic mesenchyrne and promote the proliferation of embryonic pancreatic elpithelial cells. Diabetologia 48, 277-281.
Yoshitomi, H. and Zaret, K. S. (2004). Enclothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development 131, 807-817.
Zecchin, E., Mavropoulos, A., Devos, N., Filippi, A., Tiso, N., Meyer D., Peers, B., Bortolussi, M. and Argenton, F. (2004). Evolutionary conserved role of ptf1a in the specification of exocrine pancreatic fates. Dev. Biol. 268, 174-184.
Zhang, X., Rowan, S., Yue, Y., Heaney, S., Pan, Y., Brendolan, A., Selleri, L. and Maas, R. L. (2006). Pax6 is regulated by Meis and Pbx homeoproteins during pancreatic development. Dev. Biol. 300, 748-757.
