Gadue, P., T.L. Huber, P.J. Paddison, and G.M. Keller. 2006. Wnt and TGF-beta signal<strong>in</strong>g are requiredfor <strong>the</strong> <strong>in</strong>duction <strong>of</strong> an <strong>in</strong> vitro model <strong>of</strong> primitive streak formation us<strong>in</strong>g embryonic stem <strong>cells</strong>.Proc Natl Acad Sci U S A 103: 16806-11.Gardner, R.L. 1983. Orig<strong>in</strong> and <strong>differentiation</strong> <strong>of</strong> extraembryonic tissues <strong>in</strong> <strong>the</strong> <strong>mouse</strong>. Int Rev ExpPathol 24: 63-133.Goldfarb, M. 2005. Fibroblast growth factor homologous factors: evolution, structure, and function.Cytok<strong>in</strong>e Growth Factor Rev 16: 215-20.Gospodarowicz, D. 1974. Localisation <strong>of</strong> a fibroblast growth factor and its effect alone and withhydrocortisone on 3T3 cell growth. Nature 249: 123-7.Grap<strong>in</strong>-Botton, A. and D.A. Melton. 2000. Endoderm development: from pattern<strong>in</strong>g to organogenesis.Trends Genet 16: 124-30.Groth, C. and M. Lardelli. 2002. The structure and function <strong>of</strong> vertebrate fibroblast growth factorreceptor 1. Int J Dev Biol 46: 393-400.Guo, G., J. Yang, J. Nichols, J.S. Hall, I. Eyres, W. Mansfield, and A. Smith. 2009. Klf4 revertsdevelopmentally programmed restriction <strong>of</strong> ground state pluripotency. Development 136: 1063-9.Hacohen, N., S. Kramer, D. Su<strong>the</strong>rland, Y. Hiromi, and M.A. Krasnow. 1998. sprouty encodes a novelantagonist <strong>of</strong> <strong>FGF</strong> signal<strong>in</strong>g that patterns apical branch<strong>in</strong>g <strong>of</strong> <strong>the</strong> Drosophila airways. Cell 92:253-63.Hanneken, A. 2001. Structural characterization <strong>of</strong> <strong>the</strong> circulat<strong>in</strong>g soluble <strong>FGF</strong> receptors reveals multipleis<strong>of</strong>orms generated by secretion and ectodoma<strong>in</strong> shedd<strong>in</strong>g. FEBS Lett 489: 176-81.Hardikar, A.A. 2004. Generat<strong>in</strong>g new pancreas from old. Trends Endocr<strong>in</strong>ol Metab 15: 198-203.Haub, O. and M. Goldfarb. 1991. Expression <strong>of</strong> <strong>the</strong> fibroblast growth factor-5 gene <strong>in</strong> <strong>the</strong> <strong>mouse</strong>embryo. Development 112: 397-406.Hebert, J.M., M. Boyle, and G.R. Mart<strong>in</strong>. 1991. mRNA localization studies suggest that mur<strong>in</strong>e <strong>FGF</strong>-5plays a role <strong>in</strong> gastrulation. Development 112: 407-15.Hebrok, M., S.K. Kim, and D.A. Melton. 1998. Notochord repression <strong>of</strong> endodermal Sonic hedgehogpermits pancreas development. Genes Dev 12: 1705-13.Hoerbelt, R. and J.C. Madsen. 2004. Feasibility <strong>of</strong> xeno-transplantation. Surg Cl<strong>in</strong> North Am 84: 289-307.Holland, A.M., S.J. Micallef, X. Li, A.G. Elefanty, and E.G. Stanley. 2006. A <strong>mouse</strong> carry<strong>in</strong>g <strong>the</strong> greenfluorescent prote<strong>in</strong> gene targeted to <strong>the</strong> Pdx1 locus facilitates <strong>the</strong> study <strong>of</strong> pancreas developmentand function. Genesis 44: 304-7.Hsu, Y.R., R. Nybo, J.K. Sullivan, V. Costigan, C.S. Spahr, C. Wong, M. Jones, A.G. Pentzer, J.A.Crouse, R.E. Pacifici, H.S. Lu, C.F. Morris, and J.S. Philo. 1999. Hepar<strong>in</strong> is essential for as<strong>in</strong>gle kerat<strong>in</strong>ocyte growth factor molecule to b<strong>in</strong>d and form a complex with two molecules <strong>of</strong><strong>the</strong> extracellular doma<strong>in</strong> <strong>of</strong> its receptor. Biochemistry 38: 2523-34.Itoh, N. and D.M. Ornitz. 2004. Evolution <strong>of</strong> <strong>the</strong> Fgf and Fgfr gene families. Trends Genet 20: 563-9.-. 2008. Functional evolutionary history <strong>of</strong> <strong>the</strong> <strong>mouse</strong> Fgf gene family. Dev Dyn 237: 18-27.Johannesson, M., A. Stahlberg, J. Ameri, F.W. Sand, K. Norrman, and H. Semb. 2009. <strong>FGF</strong>4 andret<strong>in</strong>oic acid direct <strong>differentiation</strong> <strong>of</strong> h<strong>ES</strong>Cs <strong>in</strong>to PDX1-express<strong>in</strong>g foregut endoderm <strong>in</strong> a timeandconcentration-dependent manner. PLoS One 4: e4794.Johnson, D.E., P.L. Lee, J. Lu, and L.T. Williams. 1990. Diverse forms <strong>of</strong> a receptor for acidic and basicfibroblast growth factors. Mol Cell Biol 10: 4728-36.Johnson, D.E., J. Lu, H. Chen, S. Werner, and L.T. Williams. 1991. The human fibroblast growth factorreceptor genes: a common structural arrangement underlies <strong>the</strong> mechanisms for generat<strong>in</strong>greceptor forms that differ <strong>in</strong> <strong>the</strong>ir third immunoglobul<strong>in</strong> doma<strong>in</strong>. Mol Cell Biol 11: 4627-34.Johnson, D.E. and L.T. Williams. 1993. Structural and functional diversity <strong>in</strong> <strong>the</strong> <strong>FGF</strong> receptormultigene family. Adv Cancer Res 60: 1-41.Jonsson, J., L. Carlsson, T. Edlund, and H. Edlund. 1994. Insul<strong>in</strong>-promoter-factor 1 is required forpancreas development <strong>in</strong> mice. Nature 371: 606-9.Jorgensen, M.C., J. Ahnfelt-Ronne, J. Hald, O.D. Madsen, P. Serup, and J. Hecksher-Sorensen. 2007.An illustrated review <strong>of</strong> early pancreas development <strong>in</strong> <strong>the</strong> <strong>mouse</strong>. Endocr Rev 28: 685-705.Kanai-Azuma, M., Y. Kanai, J.M. Gad, Y. Tajima, C. Taya, M. Kurohmaru, Y. Sanai, H. Yonekawa, K.Yazaki, P.P. Tam, and Y. Hayashi. 2002. Depletion <strong>of</strong> def<strong>in</strong>itive gut endoderm <strong>in</strong> Sox17-nullmutant mice. Development 129: 2367-79.Kharitonenkov, A., T.L. Shiyanova, A. Koester, A.M. Ford, R. Micanovic, E.J. Galbreath, G.E.Sandusky, L.J. Hammond, J.S. Moyers, R.A. Owens, J. Gromada, J.T. Broz<strong>in</strong>ick, E.D.94
Hawk<strong>in</strong>s, V.J. Wroblewski, D.S. Li, F. Mehrbod, S.R. Jaskunas, and A.B. Shanafelt. 2005.<strong>FGF</strong>-21 as a novel metabolic regulator. J Cl<strong>in</strong> Invest 115: 1627-35.K<strong>in</strong>der, S.J., T.E. Tsang, G.A. Qu<strong>in</strong>lan, A.K. Hadjantonakis, A. Nagy, and P.P. Tam. 1999. The orderlyallocation <strong>of</strong> mesodermal <strong>cells</strong> to <strong>the</strong> extraembryonic structures and <strong>the</strong> anteroposterior axisdur<strong>in</strong>g gastrulation <strong>of</strong> <strong>the</strong> <strong>mouse</strong> embryo. Development 126: 4691-701.K<strong>in</strong>der, S.J., T.E. Tsang, M. Wakamiya, H. Sasaki, R.R. Behr<strong>in</strong>ger, A. Nagy, and P.P. Tam. 2001. Theorganizer <strong>of</strong> <strong>the</strong> <strong>mouse</strong> gastrula is composed <strong>of</strong> a dynamic population <strong>of</strong> progenitor <strong>cells</strong> for <strong>the</strong>axial mesoderm. Development 128: 3623-34.Kispert, A. and B.G. Herrmann. 1994. Immunohistochemical analysis <strong>of</strong> <strong>the</strong> Brachyury prote<strong>in</strong> <strong>in</strong> wildtypeand mutant <strong>mouse</strong> embryos. Dev Biol 161: 179-93.Kraushaar, D.C., Y. Yamaguchi, and L. Wang. 2010. Heparan sulfate is required for embryonic stem<strong>cells</strong> to exit from self-renewal. J Biol Chem 285: 5907-16.Kroon, E., L.A. Mart<strong>in</strong>son, K. Kadoya, A.G. Bang, O.G. Kelly, S. Eliazer, H. Young, M. Richardson,N.G. Smart, J. Cunn<strong>in</strong>gham, A.D. Agulnick, K.A. D'Amour, M.K. Carpenter, and E.E. Baetge.2008. Pancreatic endoderm derived from human embryonic stem <strong>cells</strong> generates glucoseresponsive<strong>in</strong>sul<strong>in</strong>-secret<strong>in</strong>g <strong>cells</strong> <strong>in</strong> vivo. Nat Biotechnol 26: 443-52.Kubo, A., K. Sh<strong>in</strong>ozaki, J.M. Shannon, V. Kousk<strong>of</strong>f, M. Kennedy, S. Woo, H.J. Fehl<strong>in</strong>g, and G. Keller.2004. Development <strong>of</strong> def<strong>in</strong>itive endoderm from embryonic stem <strong>cells</strong> <strong>in</strong> culture. Development131: 1651-62.Kumar, M. and D. Melton. 2003. Pancreas specification: a budd<strong>in</strong>g question. Curr Op<strong>in</strong> Genet Dev 13:401-7.Kunath, T., M.K. Saba-El-Leil, M. Almousailleakh, J. Wray, S. Meloche, and A. Smith. 2007. <strong>FGF</strong>stimulation <strong>of</strong> <strong>the</strong> Erk1/2 <strong>signall<strong>in</strong>g</strong> cascade triggers transition <strong>of</strong> pluripotent embryonic stem<strong>cells</strong> from self-renewal to l<strong>in</strong>eage commitment. Development 134: 2895-902.Kwon, G.S., M. Viotti, and A.K. Hadjantonakis. 2008. The endoderm <strong>of</strong> <strong>the</strong> <strong>mouse</strong> embryo arises bydynamic widespread <strong>in</strong>tercalation <strong>of</strong> embryonic and extraembryonic l<strong>in</strong>eages. Dev Cell 15: 509-20.Lardon, J., S. De Breuck, I. Rooman, L. Van Lommel, M. Kruh<strong>of</strong>fer, T. Ornt<strong>of</strong>t, F. Schuit, and L.Bouwens. 2004. Plasticity <strong>in</strong> <strong>the</strong> adult rat pancreas: trans<strong>differentiation</strong> <strong>of</strong> exocr<strong>in</strong>e tohepatocyte-like <strong>cells</strong> <strong>in</strong> primary culture. Hepatology 39: 1499-507.Lawson, K.A., N.R. Dunn, B.A. Roelen, L.M. Ze<strong>in</strong>stra, A.M. Davis, C.V. Wright, J.P. Korv<strong>in</strong>g, andB.L. Hogan. 1999. Bmp4 is required for <strong>the</strong> generation <strong>of</strong> primordial germ <strong>cells</strong> <strong>in</strong> <strong>the</strong> <strong>mouse</strong>embryo. Genes Dev 13: 424-36.Lawson, K.A., J.J. Meneses, and R.A. Pedersen. 1991. Clonal analysis <strong>of</strong> epiblast fate dur<strong>in</strong>g germ layerformation <strong>in</strong> <strong>the</strong> <strong>mouse</strong> embryo. Development 113: 891-911.Lernmark, A. and A. Falorni. 1998. Immune phenomena and events <strong>in</strong> <strong>the</strong> islets <strong>in</strong> <strong>in</strong>sul<strong>in</strong>-dependentdiabetes mellitus. In Textbook <strong>of</strong> Diabetes (ed. J.C. Pickup and G. Williams). BlackwellAcience Ltd., Oxford.Li, M., L. Pevny, R. Lovell-Badge, and A. Smith. 1998. Generation <strong>of</strong> purified neural precursors fromembryonic stem <strong>cells</strong> by l<strong>in</strong>eage selection. Curr Biol 8: 971-4.Li, P.M. and B.J. Goldste<strong>in</strong>. 1996. Cell density-dependent changes <strong>in</strong> <strong>the</strong> <strong>in</strong>sul<strong>in</strong> action pathway:evidence for <strong>in</strong>volvement <strong>of</strong> prote<strong>in</strong>-tyros<strong>in</strong>e phosphatases. J Cell Biochem 61: 31-8.Lim, J., P. Yus<strong>of</strong>f, E.S. Wong, S. Chandramouli, D.H. Lao, C.W. Fong, and G.R. Guy. 2002. Thecyste<strong>in</strong>e-rich sprouty translocation doma<strong>in</strong> targets mitogen-activated prote<strong>in</strong> k<strong>in</strong>ase <strong>in</strong>hibitoryprote<strong>in</strong>s to phosphatidyl<strong>in</strong>ositol 4,5-bisphosphate <strong>in</strong> plasma membranes. Mol Cell Biol 22:7953-66.L<strong>in</strong>g, C. and L. Groop. 2009. Epigenetics: a molecular l<strong>in</strong>k between environmental factors and type 2diabetes. Diabetes 58: 2718-25.Liu, D., H. Chu, L. Maves, Y.L. Yan, P.A. Morcos, J.H. Postlethwait, and M. Westerfield. 2003. Fgf3and Fgf8 dependent and <strong>in</strong>dependent transcription factors are required for otic placodespecification. Development 130: 2213-24.Liu, P., M. Wakamiya, M.J. Shea, U. Albrecht, R.R. Behr<strong>in</strong>ger, and A. Bradley. 1999. Requirement forWnt3 <strong>in</strong> vertebrate axis formation. Nat Genet 22: 361-5.Liu, Z., J. Xu, J.S. Colv<strong>in</strong>, and D.M. Ornitz. 2002. Coord<strong>in</strong>ation <strong>of</strong> chondrogenesis and osteogenesis byfibroblast growth factor 18. Genes Dev 16: 859-69.Ma, Y.G., E. Rosfjord, C. Huebert, P. Wilder, J. Tiesman, D. Kelly, and A. Rizz<strong>in</strong>o. 1992.Transcriptional regulation <strong>of</strong> <strong>the</strong> mur<strong>in</strong>e k-<strong>FGF</strong> gene <strong>in</strong> embryonic cell l<strong>in</strong>es. Dev Biol 154: 45-54.Madsen, O.D. 2005. Stem <strong>cells</strong> and diabetes treatment. Apmis 113: 858-75.95
- Page 1:
PhD thesisCand.scient. Janny Marie
- Page 5:
ResuméSukkersyge er en sygdom der
- Page 9:
Table of contents1
- Page 12 and 13:
ICMinner cell massIdInhibitor of di
- Page 14 and 15:
cell mass regenerates probably thro
- Page 16 and 17:
Figure 1-1: Early embryo developmen
- Page 18 and 19:
Figure 1-3: Regional expression of
- Page 20 and 21:
The pluripotent stateThe pluripoten
- Page 25 and 26:
There are four membrane-bound FGFRs
- Page 27:
2. AimsThe aim of this study was to
- Page 30 and 31:
Developmental Biology 330 (2009) 28
- Page 32 and 33:
288 M. Hansson et al. / Development
- Page 34 and 35:
290 M. Hansson et al. / Development
- Page 36 and 37:
292 M. Hansson et al. / Development
- Page 38 and 39:
294 M. Hansson et al. / Development
- Page 40 and 41:
296 M. Hansson et al. / Development
- Page 42 and 43:
298 M. Hansson et al. / Development
- Page 44 and 45:
300 M. Hansson et al. / Development
- Page 46 and 47:
302 M. Hansson et al. / Development
- Page 48 and 49:
304 M. Hansson et al. / Development
- Page 50 and 51: Figure S2Figure S2: A subpopulation
- Page 52 and 53: Figure S4Figure S4: Expression of T
- Page 54 and 55: Figure S6Figure S6: qRT-PCR analyse
- Page 56 and 57: epithelium; Cdx2, expressed posteri
- Page 58 and 59: Figure 4-4: A high FGF4-concentrati
- Page 60 and 61: Figure 4-6: A 3-step protocol does
- Page 63 and 64: 5. Paper IIFGFR(IIIc)-activation in
- Page 65 and 66: AbstractProgress in embryonic stem
- Page 67 and 68: variants in their Ig-like domain II
- Page 69 and 70: Cell count and proliferation assayC
- Page 71 and 72: influence on the numbers of Sox17-G
- Page 73 and 74: undifferentiated cells, we found th
- Page 75 and 76: FGF4, 5, FGF8b and FGFR1, are expre
- Page 77 and 78: with EdU-stain (blue sample); and w
- Page 79 and 80: Olsen, S.K., J.Y. Li, C. Bromleigh,
- Page 81 and 82: FiguresFigure 1: Screen for FGFR-is
- Page 83 and 84: Figure 3: Activation of FGFRb or FG
- Page 87 and 88: Opposite, Figure 6: In the absence
- Page 89 and 90: 6. General discussionEndoderm diffe
- Page 91 and 92: Overall, the multitude of FGF-signa
- Page 93 and 94: transplantation is the spread of an
- Page 96: AcknowledgementsThe work presented
- Page 99: Chambers, I., D. Colby, M. Robertso
- Page 103 and 104: Nishikawa, S.I., S. Nishikawa, M. H
- Page 105 and 106: Tanimizu, N., H. Saito, K. Mostov,