Rodaway, A. and R. Patient. 2001. Mesendoderm. an ancient germ layer? Cell 105: 169-72.Rodaway, A., H. Takeda, S. Koshida, J. Broadbent, B. Price, J.C. Smith, R. Patient, and N. Holder.1999. Induction <strong>of</strong> <strong>the</strong> mesendoderm <strong>in</strong> <strong>the</strong> zebrafish germ r<strong>in</strong>g by yolk cell-derived TGF-betafamily signals and discrim<strong>in</strong>ation <strong>of</strong> mesoderm and endoderm by <strong>FGF</strong>. Development 126: 3067-78.Rossant, J. 2004. L<strong>in</strong>eage development and polar asymmetries <strong>in</strong> <strong>the</strong> peri-implantation <strong>mouse</strong> blastocyst.Sem<strong>in</strong> Cell Dev Biol 15: 573-81.Rossi, J.M., N.R. Dunn, B.L. Hogan, and K.S. Zaret. 2001. Dist<strong>in</strong>ct mesodermal signals, <strong>in</strong>clud<strong>in</strong>gBMPs from <strong>the</strong> septum transversum mesenchyme, are required <strong>in</strong> comb<strong>in</strong>ation forhepatogenesis from <strong>the</strong> endoderm. Genes Dev 15: 1998-2009.Ross<strong>in</strong>i, A.A., D.L. Gre<strong>in</strong>er, and J.P. Mordes. 1999. Induction <strong>of</strong> immunologic tolerance fortransplantation. Physiol Rev 79: 99-141.Ryan, E.A., B.W. Paty, P.A. Senior, D. Bigam, E. Alfadhli, N.M. Kneteman, J.R. Lakey, and A.M.Shapiro. 2005. Five-year follow-up after cl<strong>in</strong>ical islet transplantation. Diabetes 54: 2060-9.Schroeder, I.S., A. Rolletschek, P. Blyszczuk, G. Kania, and A.M. Wobus. 2006. Differentiation <strong>of</strong><strong>mouse</strong> embryonic stem <strong>cells</strong> to <strong>in</strong>sul<strong>in</strong>-produc<strong>in</strong>g <strong>cells</strong>. Nat Protoc 1: 495-507.Seaberg, R.M., S.R. Smukler, T.J. Kieffer, G. Enikolopov, Z. Asghar, M.B. Wheeler, G. Korbutt, and D.van der Kooy. 2004. Clonal identification <strong>of</strong> multipotent precursors from adult <strong>mouse</strong> pancreasthat generate neural and pancreatic l<strong>in</strong>eages. Nat Biotechnol 22: 1115-24.Segu<strong>in</strong>, C.A., J.S. Draper, A. Nagy, and J. Rossant. 2008. Establishment <strong>of</strong> endoderm progenitors bySOX transcription factor expression <strong>in</strong> human embryonic stem <strong>cells</strong>. Cell Stem Cell 3: 182-95.Semb, H. 2008. Def<strong>in</strong>itive endoderm: a key step <strong>in</strong> coax<strong>in</strong>g human embryonic stem <strong>cells</strong> <strong>in</strong>totransplantable beta-<strong>cells</strong>. Biochem Soc Trans 36: 272-5.Shapiro, A.M., J.R. Lakey, E.A. Ryan, G.S. Korbutt, E. Toth, G.L. Warnock, N.M. Kneteman, and R.V.Rajotte. 2000. Islet transplantation <strong>in</strong> seven patients with type 1 diabetes mellitus us<strong>in</strong>g aglucocorticoid-free immunosuppressive regimen. N Engl J Med 343: 230-8.Sherwood, R.I., C. Jitianu, O. Cleaver, D.A. Shaywitz, J.O. Lamenzo, A.E. Chen, T.R. Golub, and D.A.Melton. 2007. Prospective isolation and global gene expression analysis <strong>of</strong> def<strong>in</strong>itive andvisceral endoderm. Dev Biol 304: 541-55.S<strong>in</strong>gh, R.K., N. Llansa, C.D. Bucana, R. Sanchez, A. Koura, and I.J. Fidler. 1996. Cell densitydependentregulation <strong>of</strong> basic fibroblast growth factor expression <strong>in</strong> human renal cell carc<strong>in</strong>oma<strong>cells</strong>. Cell Growth Differ 7: 397-404.Slack, J.M. 1995. Developmental biology <strong>of</strong> <strong>the</strong> pancreas. Development 121: 1569-80.Smith, A.G., J.K. Heath, D.D. Donaldson, G.G. Wong, J. Moreau, M. Stahl, and D. Rogers. 1988.Inhibition <strong>of</strong> pluripotential embryonic stem cell <strong>differentiation</strong> by purified polypeptides. Nature336: 688-90.Smith, A.G., J. Nichols, M. Robertson, and P.D. Rathjen. 1992. Differentiation <strong>in</strong>hibit<strong>in</strong>g activity(DIA/LIF) and <strong>mouse</strong> development. Dev Biol 151: 339-51.Solter, D. and B.B. Knowles. 1978. Monoclonal antibody def<strong>in</strong><strong>in</strong>g a stage-specific <strong>mouse</strong> embryonicantigen (SSEA-1). Proc Natl Acad Sci U S A 75: 5565-9.Stavridis, M.P., J.S. Lunn, B.J. Coll<strong>in</strong>s, and K.G. Storey. 2007. A discrete period <strong>of</strong> <strong>FGF</strong>-<strong>in</strong>duced Erk1/2<strong>signall<strong>in</strong>g</strong> is required for vertebrate neural specification. Development 134: 2889-94.Strumpf, D., C.A. Mao, Y. Yamanaka, A. Ralston, K. Chawengsaksophak, F. Beck, and J. Rossant.2005. Cdx2 is required for correct cell fate specification and <strong>differentiation</strong> <strong>of</strong> trophectoderm <strong>in</strong><strong>the</strong> <strong>mouse</strong> blastocyst. Development 132: 2093-102.Sun, X., E.N. Meyers, M. Lewandoski, and G.R. Mart<strong>in</strong>. 1999. Targeted disruption <strong>of</strong> Fgf8 causesfailure <strong>of</strong> cell migration <strong>in</strong> <strong>the</strong> gastrulat<strong>in</strong>g <strong>mouse</strong> embryo. Genes Dev 13: 1834-46.Tada, S., T. Era, C. Furusawa, H. Sakurai, S. Nishikawa, M. K<strong>in</strong>oshita, K. Nakao, and T. Chiba. 2005.Characterization <strong>of</strong> mesendoderm: a diverg<strong>in</strong>g po<strong>in</strong>t <strong>of</strong> <strong>the</strong> def<strong>in</strong>itive endoderm and mesoderm<strong>in</strong> embryonic stem cell <strong>differentiation</strong> culture. Development 132: 4363-74.Takahashi, K., K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda, and S. Yamanaka. 2007.Induction <strong>of</strong> pluripotent stem <strong>cells</strong> from adult human fibroblasts by def<strong>in</strong>ed factors. Cell 131:861-72.Takahashi, K. and S. Yamanaka. 2006. Induction <strong>of</strong> pluripotent stem <strong>cells</strong> from <strong>mouse</strong> embryonic andadult fibroblast cultures by def<strong>in</strong>ed factors. Cell 126: 663-76.Tam, P.P. and R.S. Bedd<strong>in</strong>gton. 1992. Establishment and organization <strong>of</strong> germ layers <strong>in</strong> <strong>the</strong> gastrulat<strong>in</strong>g<strong>mouse</strong> embryo. Ciba Found Symp 165: 27-41; discussion 42-9.Tam, P.P., E.A. Williams, and W.Y. Chan. 1993. Gastrulation <strong>in</strong> <strong>the</strong> <strong>mouse</strong> embryo: ultrastructural andmolecular aspects <strong>of</strong> germ layer morphogenesis. Microsc Res Tech 26: 301-28.98
Tanimizu, N., H. Saito, K. Mostov, and A. Miyajima. 2004. Long-term culture <strong>of</strong> hepatic progenitorsderived from <strong>mouse</strong> Dlk+ hepatoblasts. J Cell Sci 117: 6425-34.Tesar, P.J., J.G. Chenoweth, F.A. Brook, T.J. Davies, E.P. Evans, D.L. Mack, R.L. Gardner, and R.D.McKay. 2007. New cell l<strong>in</strong>es from <strong>mouse</strong> epiblast share def<strong>in</strong><strong>in</strong>g features with humanembryonic stem <strong>cells</strong>. Nature 448: 196-9.Thomson, J.A., J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.S. Marshall, and J.M.Jones. 1998. Embryonic stem cell l<strong>in</strong>es derived from human blastocysts. Science 282: 1145-7.Toml<strong>in</strong>son, E., L. Fu, L. John, B. Hultgren, X. Huang, M. Renz, J.P. Stephan, S.P. Tsai, L. Powell-Braxton, D. French, and T.A. Stewart. 2002. Transgenic mice express<strong>in</strong>g human fibroblastgrowth factor-19 display <strong>in</strong>creased metabolic rate and decreased adiposity. Endocr<strong>in</strong>ology 143:1741-7.Touboul, T., N.R. Hannan, S. Corb<strong>in</strong>eau, A. Mart<strong>in</strong>ez, C. Mart<strong>in</strong>et, S. Branchereau, S. Ma<strong>in</strong>ot, H.Strick-Marchand, R. Pedersen, J. Di Santo, A. Weber, and L. Vallier. 2009. Generation <strong>of</strong>functional hepatocytes from human embryonic stem <strong>cells</strong> under chemically def<strong>in</strong>ed conditionsthat recapitulate liver development. Hepatology.Tzouanacou, E., A. Wegener, F.J. Wymeersch, V. Wilson, and J.F. Nicolas. 2009. Redef<strong>in</strong><strong>in</strong>g <strong>the</strong>progression <strong>of</strong> l<strong>in</strong>eage segregations dur<strong>in</strong>g mammalian embryogenesis by clonal analysis. DevCell 17: 365-76.Umehara, H., T. Kimura, S. Ohtsuka, T. Nakamura, K. Kitajima, M. Ikawa, M. Okabe, H. Niwa, and T.Nakano. 2007. Efficient derivation <strong>of</strong> embryonic stem <strong>cells</strong> by <strong>in</strong>hibition <strong>of</strong> glycogen synthasek<strong>in</strong>ase-3. Stem Cells 25: 2705-11.Va<strong>in</strong>ikka, S., J. Partanen, P. Bellosta, F. Coulier, D. Birnbaum, C. Basilico, M. Jaye, and K. Alitalo.1992. Fibroblast growth factor receptor-4 shows novel features <strong>in</strong> genomic structure, ligandb<strong>in</strong>d<strong>in</strong>g and signal transduction. Embo J 11: 4273-80.Vallier, L., D. Reynolds, and R.A. Pedersen. 2004. Nodal <strong>in</strong>hibits <strong>differentiation</strong> <strong>of</strong> human embryonicstem <strong>cells</strong> along <strong>the</strong> neuroectodermal default pathway. Dev Biol 275: 403-21.Vallier, L., T. Touboul, Z. Chng, M. Brimpari, N. Hannan, E. Millan, L.E. Smi<strong>the</strong>rs, M. Trotter, P.Rugg-Gunn, A. Weber, and R.A. Pedersen. 2009. Early cell fate decisions <strong>of</strong> human embryonicstem <strong>cells</strong> and <strong>mouse</strong> epiblast stem <strong>cells</strong> are controlled by <strong>the</strong> same <strong>signall<strong>in</strong>g</strong> pathways. PLoSOne 4: e6082.Van Ho<strong>of</strong>, D., K.A. D'Amour, and M.S. German. 2009. Derivation <strong>of</strong> <strong>in</strong>sul<strong>in</strong>-produc<strong>in</strong>g <strong>cells</strong> fromhuman embryonic stem <strong>cells</strong>. Stem Cell Res 3: 73-87.Walshe, J. and I. Mason. 2003. Unique and comb<strong>in</strong>atorial functions <strong>of</strong> Fgf3 and Fgf8 dur<strong>in</strong>g zebrafishforebra<strong>in</strong> development. Development 130: 4337-49.Wandzioch, E. and K.S. Zaret. 2009. Dynamic signal<strong>in</strong>g network for <strong>the</strong> specification <strong>of</strong> embryonicpancreas and liver progenitors. Science 324: 1707-10.Wang, X. and K. Ye. 2009. Three-dimensional <strong>differentiation</strong> <strong>of</strong> embryonic stem <strong>cells</strong> <strong>in</strong>to islet-like<strong>in</strong>sul<strong>in</strong>-produc<strong>in</strong>g clusters. Tissue Eng Part A 15: 1941-52.Wasylyk, B., J. Hagman, and A. Gutierrez-Hartmann. 1998. Ets transcription factors: nuclear effectors<strong>of</strong> <strong>the</strong> Ras-MAP-k<strong>in</strong>ase signal<strong>in</strong>g pathway. Trends Biochem Sci 23: 213-6.Watanabe, K., D. Kamiya, A. Nishiyama, T. Katayama, S. Nozaki, H. Kawasaki, Y. Watanabe, K.Mizuseki, and Y. Sasai. 2005. Directed <strong>differentiation</strong> <strong>of</strong> telencephalic precursors fromembryonic stem <strong>cells</strong>. Nat Neurosci 8: 288-96.Wells, J.M. and D.A. Melton. 1999. Vertebrate endoderm development. Annu Rev Cell Dev Biol 15:393-410.-. 2000. Early <strong>mouse</strong> endoderm is patterned by soluble factors from adjacent germ layers. Development127: 1563-72.Wilk<strong>in</strong>son, D.G., G. Peters, C. Dickson, and A.P. McMahon. 1988. Expression <strong>of</strong> <strong>the</strong> <strong>FGF</strong>-related protooncogene<strong>in</strong>t-2 dur<strong>in</strong>g gastrulation and neurulation <strong>in</strong> <strong>the</strong> <strong>mouse</strong>. Embo J 7: 691-5.Willems, E. and L. Leyns. 2008. Pattern<strong>in</strong>g <strong>of</strong> <strong>mouse</strong> embryonic stem cell-derived pan-mesoderm byActiv<strong>in</strong> A/Nodal and Bmp4 signal<strong>in</strong>g requires Fibroblast Growth Factor activity. Differentiation76: 745-59.Xu, J., Z. Liu, and D.M. Ornitz. 2000. Temporal and spatial gradients <strong>of</strong> Fgf8 and Fgf17 regulateproliferation and <strong>differentiation</strong> <strong>of</strong> midl<strong>in</strong>e cerebellar structures. Development 127: 1833-43.Xu, X., J. D'Hoker, G. Stange, S. Bonne, N. De Leu, X. Xiao, M. Van de Casteele, G. Mellitzer, Z. L<strong>in</strong>g,D. Pipeleers, L. Bouwens, R. Scharfmann, G. Gradwohl, and H. Heimberg. 2008. Beta <strong>cells</strong> canbe generated from endogenous progenitors <strong>in</strong> <strong>in</strong>jured adult <strong>mouse</strong> pancreas. Cell 132: 197-207.Yamaguchi, T.P., K. Harpal, M. Henkemeyer, and J. Rossant. 1994. fgfr-1 is required for embryonicgrowth and mesodermal pattern<strong>in</strong>g dur<strong>in</strong>g <strong>mouse</strong> gastrulation. Genes Dev 8: 3032-44.99
- 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 and 100: Chambers, I., D. Colby, M. Robertso
- Page 101 and 102: Hawkins, V.J. Wroblewski, D.S. Li,
- Page 103: Nishikawa, S.I., S. Nishikawa, M. H