Mesoderm induction: From caps to chips

Nature Reviews Genetics

Volumn 7, Issue 5, 2006, Pages 360-372

  Kimelman, David ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN; BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; FIBROBLAST GROWTH FACTOR 3; FIBROBLAST GROWTH FACTOR 4; FIBROBLAST GROWTH FACTOR 8; OSTEOGENIC PROTEIN 1; PROTEIN ADMP; PROTEIN GDF3; PROTEIN VG1; PROTEIN XNR1; PROTEIN XNR2; PROTEIN XNR4; PROTEIN XNR5; PROTEIN XNR6; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR; UNCLASSIFIED DRUG; WNT3 PROTEIN; WNT3A PROTEIN; WNT8 PROTEIN; WNT8C PROTEIN;

CELL FATE; HIGH THROUGHPUT SCREENING; MESODERM; MICROARRAY ANALYSIS; MORPHOGENESIS; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; VERTEBRATE; XENOPUS; ZEBRA FISH;

ANIMALS; BODY PATTERNING; CHICKENS; EMBRYONIC INDUCTION; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GLYCOPROTEINS; MEMBRANE PROTEINS; MESODERM; MICE; MODELS, BIOLOGICAL; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA; WNT PROTEINS; XENOPUS; XENOPUS PROTEINS; ZEBRAFISH; ZEBRAFISH PROTEINS;

DANIO RERIO; VERTEBRATA;

EID: 33646172661     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/nrg1837     Document Type: Review

References (126)

1. Nieuwkoop, P. D. The formation of the mesoderm in urodelean amphibians I. The induction by the endoderm. W. Roux' Arch. Ent. Org. 162, 341-373 (1969). This paper provided crucial evidence that the mesoderm in amphibians is produced by an inductive event.
2. Niehrs, C. Regionally specific induction by the Spemann-Mangold organizer. Nature Rev. Genet. 5, 425-434 (2004).
3. Kimelman, D. & Bjornson, C. in Gastrulation (ed. Stern, C. D.) 363-372 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004).
4. Harland, R. M. in Gastrulation (ed. Stern, C. D.) 373-388 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004).
5. Warga, R. M. & Nüsslein-Volhard, C. Origin and development of the zebrafish endoderm. Development 126, 827-838 (1999).
6. Kimmel, C. B., Warga, R. M. & Schilling, T. F. Origin and organization of the zebrafish fate map. Development 108, 581-594 (1990).
7. Wardle, F. C. & Smith, J. C. Refinement of gene expression patterns in the early Xenopus embryo. Development 131, 4687-4696 (2004).
8. Slack, J. M. W., Darlington, B. G., Heath, J. K. & Godsave, S. F. Mesoderm induction in early Xenopus embryos by heparin-binding growth factors. Nature 326, 197-200 (1987).
9. Kimelman, D. & Kirschner, M. Synergistic induction of mesoderm by FGF and TGF-β and the identification of an mRNA coding for FGF in the early Xenopus embryo. Cell 51, 869-877 (1987). Together with reference 8, these studies were the first to identify a specific protein as a mesoderm-inducing agent, in this case FGF.
10. Kelly, G. M., Greenstein, P., Erezyilmaz, D. F. & Moon, R. T. Zebrafish wnt8 and wnt8b share a common activity but are involved in distinct developmental pathways. Development 121, 1787-1799 (1995).
11. Szeto, D. P. & Kimelman, D. Combinatorial gene regulation by Bmp and Wnt in zebrafish posterior mesoderm formation. Development 131, 3751-3760 (2004).
12. Dale, L., Howes, G., Price, B. M. J. & Smith, J. C. Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. Development 115, 573-585 (1992).
13. Köster, M. et al. Bone morphogenetic protein 4 (BMP-4), a member of the TGF-β family in early embryos of Xenopus laevis: analysis of mesoderm inducing activity. Mech. Dev. 33, 191-200 (1991).
14. Gritsman, K., Talbot, W. S. & Schier, A. F. Nodal signaling patterns the organizer. Development 127, 921-932 (2000).
15. Birsoy, B., Kofron, M., Schaible, K., Wylie, C. & Heasman, J. Vg1 is an essential signaling molecule in Xenopus development. Development 133, 15-20 (2006).
16. Smith, J. C. A mesoderm-inducing factor is produced by a Xenopus cell line. Development 99, 3-14 (1987). A seminal paper in modern mesoderm-induction research, which shows that a semi-purified factor produced by a specific cell line induces mesoderm in Xenopus animal cap explants.
17. Sivak, J. & Amaya, E. in Gastrulation (ed. Stern, C. D.) 463-474 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004).
18. Munoz-Sanjuan, I. & Hemmati-Brivanlou, A. H. in Gastrulation (ed. Stern, C. D.) 475-490 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004).
19. Houston, D. W. & Wylie, C. in Gastrulation (ed. Stern, C. D.) 521-538 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004).
20. King, M. L., Messitt, T. J. & Mowry, K. L. Putting RNAs in the right place at the right time: RNA localization in the frog oocyte. Biol. Cell 97, 19-33 (2005).
21. Hyde, C. E. & Old, R. W. Regulation of the early expression of the Xenopus nodal-related 1 gene, Xnr1. Development 127, 1221-1229 (2000).
22. Clements, D., Friday, R. V. & Woodland, H. R. Mode of action of VegT in mesoderm and endoderm formation. Development 126, 4903-4911 (1999).
23. Kofron, M. et al. Mesoderm induction in Xenopus is a zygotic event regulated by maternal VegT via TGFβ growth factors. Development 126, 5759-5770 (1999).
24. Xanthos, J. B., Kofron, M., Wylie, C. & Heasman, J. Maternal VegT is the initiator of a molecular network specifying endoderm in Xenopus laevis. Development 128, 167-180 (2001).
25. Zhang, J. et al. The role of maternal VegT in establishing the primary germ layers in Xenopus embryos. Cell 94, 515-524 (1998). Demonstration that the T-box transcription factor VegT is essential for the formation of the mesoderm (and endoderm) in Xenopus embryos.
26. Schier, A. F. & Talbot, W. S. Molecular genetics of axis formation in zebrafish. Annu. Rev. Genet. 39, 561-613 (2005).
27. Griffin, K. J. P., Amacher, S. L., Kimmel, C. B. & Kimelman, D. Molecular identification of spadetail: regulation of zebrafish trunk and tail mesoderm formation by T-box genes. Development 125, 3379-3388 (1998).
28. Weaver, C. & Kimelman, D. Move it or lose it: axis specification in Xenopus. Development 131, 3491-3499 (2004).
29. Mizuno, T., Yamaha, E., Kuroiwa, A. & Takeda, H. Removal of vegetal yolk causes dorsal deficencies and impairs dorsal-inducing ability of the yolk cell in zebrafish. Mech. Dev. 81, 51-63 (1999).
30. Ober, E. A. & Schulte-Merker, S. Signals from the yolk cell induce mesoderm, neuroectoderm, the trunk organizer, and the notochord in zebrafish. Dev. Biol. 215, 167-181 (1999).
31. McMahon, A. P. & Moon, R. T. Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis. Cell 58, 1075-1084 (1989). This work provided the first evidence that the Wnt signalling pathway has a crucial role in the formation of the Xenopus embryonic axis.
32. Heasman, J. et al. Overexpression of cadherins and underexpression of β-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. Cell 79, 791-803 (1994).
33. DeRobertis, e. M., Larrain, J., Oelgeschlager, M. & Wessely, O. The establishment of Spemann's organizer and the patterning of the vertebrate embryo. Nature Genet. 1, 171-181 (2000).
34. Yang, J., Tan, C., Darken, R. S., Wilson, P. A. & Klein, P. S. β-Catenin/Tcf-regulated transcription prior to the midblastula transition. Development 129, 5743-5752 (2002).
35. Agius, E., Oelgeschlager, M., Wessely, O., Kemp, C. & De Robertis, E. M. Endodermal Nodal-related signals and mesoderm induction in Xenopus. Development 127, 1173-1183 (2000).
36. Takahashi, S. et al. Two novel nodal-related genes initiate early inductive events in Xenopus Nieuwkoop center. Development 127, 5319-5329 (2000).
37. Schohl, A. & Fagotto, F. β-Catenin, MAPK and Smad signaling during early Xenopus development. Development 129, 37-52 (2002).
38. Faure, S., Lee, M. A., Keller, T., ten Dijke, P. & Whitman, M. Endogenous patterns of TGFβ superfamily signaling during early Xenopus development. Development 127, 2917-2931 (2000).
39. Feldman, B. et al. Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature 395, 181-185 (1998).
40. Gore, A. V. et al. The zebrafish dorsal axis is apparent at the 4-cell stage. Nature 438, 1030-1035 (2005).
41. Aoki, T. O. et al. Regulation of Nodal signalling and mesendoderm formation by TARAM-A, a TGFβ-related type I receptor. Dev. Biol. 241, 273-288 (2002).
42. Green, J. B. A., Howes, G., Symes, K., Cooke, J. & Smith, J. C. The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF. Development 108, 173-183 (1990).
43. Green, J. B. A., New, H. V. & Smith, J. C. Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell 71, 731-739 (1992).
44. McDowell, N. & Gurdon, J. B. Activin as a morphogen in Xenopus mesoderm induction. Semin. Cell Dev. Biol. 10, 311-317 (1999). A review of the important studies, particularly from the laboratories of John Gurdon, Jim Smith and Doug Melton, using Activin to study the mechanisms of mesoderm induction, including the role of Nodal family members as morphogens.
45. Dougan, S. T., Warga, R. M., Kane, D. A., Schier, A. F. & Talbot, W. S. The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm. Development 130, 1837-1851 (2003).
46. Keegan, B. R., Meyer, D. & Yelon, D. Organization of cardiac chamber progenitors in the zebrafish blastula. Development 131, 3081-3091 (2004).
47. Piepenburg, O., Grimmer, D., Williams, P. H. & Smith, J. C. Activin redux: specification of mesodermal pattern in Xenopus by graded concentrations of endogenous activin B. Development 131, 4977-4986 (2004).
48. Osada, S. I. & Wright, C. V. Xenopus nodal-related signaling is essential for mesendodermal patterning during early embryogenesis. Development 126, 3229-3240 (1999).
49. Piccolo, S. et al. The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature 397, 707-710 (1999).
50. Houston, D. W. & Wylie, C. Maternal Xenopus Zic2 negatively regulates Nodal-related gene expression during anteroposterior patterning. Development 132, 4845-4855 (2005).
51. Weeks, D. L. & Melton, D. A. A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF-β. Cell 51, 861-867 (1987). The first identification of an endogenous TGFB factor in mesoderm induction in Xenopus.
52. Kessler, D. S. in Gastrulation (ed. Stern, C. D.) 505-520 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004).
53. Shah, S. B. et al. Misexpression of chick Vg1 in the marginal zone induces primitive streak formation. Development 124, 5127-5138 (1997).
54. Skromne, I. & Stern, C. D. Interactions between Wnt and Vg1 signalling pathways initiate primitive streak formation in the chick embryo. Development 128, 2915-2927 (2001).
55. Chen, C. et al. The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo. Development 133, 319-329 (2005).
56. Hyatt, B. A. & Yost, H. J. The left-right coordinator: the role of Vg1 in organizing left-right axis formation. Cell 93, 37-46 (1998).
57. Ramsdell, A. F. & Yost, H. J. Cardiac looping and the vertebrate left-right axis: antagonism of left-sided Vg1 activity by a right-sided ALK2-dependent BMP pathway. Development 126, 5195-5205 (1999).
58. Kramer, K. L. & Yost, H. J. Ectodermal syndecan-2 mediates left-right axis formation in migrating mesoderm as a cell-nonautonomous Vg1 cofactor. Dev. Cell 2, 115-124 (2002).
59. Helde, K. A. & Grunwald, D. J. The DVR-1 (Vg1) transcript of zebrafish is maternally supplied and distributed throughout the embryo. Dev. Biol. 159, 418-426 (1993).
60. Amaya, E., Musci, T. J. & Kirschner, M. W. Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Cell 66, 257-270 (1991). The first use of a dominant-negative receptor to study mesoderm induction provided crucial evidence for a role of FGF signalling in forming the posterior body.
61. Griffin, K. J. P., Patient, R. K. & Holder, N. H. K. Analysis of FGF function in normal and no tail zebrafish embryos reveals separate mechanisms for formation of the trunk and tail. Development 121, 2983-2994 (1995).
62. Goering, L. M. et al. An interacting network of T-box genes directs gene expression and fate in the zebrafish mesoderm. Proc. Natl Acad. Sci. USA 100, 9410-9415 (2003).
63. Amacher, S. L., Draper, B. W., Summers, B. R. & Kimmel, C. B. The zebrafish T-box genes no tail and spadetail are required for development of trunk and tail mesoderm and medial floor plate. Development 129, 3311-3323 (2002).
64. Griffin, K. J. P. & Kimelman, D. Interplay between FGF, One-eyed pinhead and T-box transcription factors during zebrafish posterior development. Dev. Biol. 264, 456-466 (2003).
65. Draper, B. W., Stock, D. W. & Kimmel, C. B. Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development. Development 130, 4639-4654 (2003).
66. Isaacs, H. V., Pownal, M. E. & Slack, J. M. W. eFGF regulates Xbra expression during Xenopus gastrulation. EMBO J. 13, 4469-4481 (1994).
67. Ramel, M. C. & Lekven, A. C. Repression of the vertebrate organizer by Wnt8 is mediated by Vent and Vox. Development 131, 3991-4000 (2004).
68. Vonica, A. & Gumbiner, B. M. Zygotic Wnt activity is required for Brachyury expression in the early Xenopus laevis embryo. Dev. Biol. 250, 112-127 (2002).
69. Thorpe, C. J., Weidinger, G. & Moon, R. T. Wnt/β-catenin regulation of the Sp1-related transcription factor sp5l promotes tail development in zebrafish. Development 132, 1763-1772 (2005).
70. Lekven, A. C., Thorpe, C. J., Waxman, J. S. & Moon, R. T. Zebrafish wnt8 encodes two wnt8 proteins on a bicistronic transcript and is required for mesoderm and neurectoderm patterning. Dev. Cell 1, 103-114 (2001).
71. Smith, W. C. & Harland, R. M. Expression cloning of noggin, a new dorsalizing factor localized in the Spemann organizer in Xenopus embryos. Cell 70, 829-840 (1992).
72. Sasai, Y. et al. Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. Cell 79, 779-790 (1994). Together with reference 71, these papers report the cloning of two novel BMP inhibitors that are expressed in the organizer (Noggin and Chordin), which are essential for the function of the organizer.
73. De Robertis, E. M. & Kuroda, H. Dorsal-ventral patterning and neural induction in Xenopus embryos. Annu. Rev. Cell Dev. Biol. 20, 285-308 (2004).
74. Reversade, B., Kuroda, H., Lee, H., Mays, A. & De Robertis, E. M. Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain formation in Xenopus embryos. Development 132, 3381-3392 (2005).
75. Nguyen, V. H. et al. Ventral and lateral regions of the zebrafish gastrula, including the neural crest progenitors, are established by a bmp2b/swirl pathway of genes. Dev. Biol. 199, 93-110 (1998).
76. Kishimoto, Y., Lee, K. H., Zon, L., Hammerschmidt, M. & Schulte-Merker, S. The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning. Development 124, 4457-4466 (1997).
77. Beck, C. W, Whitman, M., Slack J. M. The role of BMP signaling in outgrowth and patterning of the Xenopus tail bud. Dev. Biol. 238, 303-314 (2001).
78. Agathon, A., Thisse, C. & Thisse, B. The molecular nature of the zebrafish tail organizer. Nature 424, 448-452 (2003).
79. Beck, C. W., Whitman, M. & Slack, J. M. The role of BMP signaling in outgrowth and patterning of the Xenopus tail bud. Dev. Biol. 238, 303-314 (2001).
80. Beck, C. W. & Slack, J. M. Analysis of the developing Xenopus tail bud reveals separate phases of gene expression during determination and outgrowth. Mech. Dev. 72, 41-52 (1998).
81. Beck, C. W. & Slack, J. M. A developmental pathway controlling outgrowth of the Xenopus tail bud. Development 126, 1611-1620 (1999).
82. Beck, C. W. & Slack, J. M. Notch is required for outgrowth of the Xenopus tail bud. Int. J. Dev. Biol. 46, 255-258 (2002).
83. Gritsman, K. et al. The EGF-CFC protein one-eyed pinhead is essential for Nodal signaling. Cell 97, 121-132 (1999). This study demonstrates that the EGF-CFC protein Oep is essential for the formation of all endoderm and most mesoderm because Oep is required for Nodal signalling.
84. Lele, Z., Nowak, M. & Hammerschmidt, M. Zebrafish admp is required to restrict the size of the organizer and to promote posterior and ventral development. Dev. Dyn. 222, 681-687 (2001).
85. Willot, V. et al. Cooperative action of ADMP- and BMP-mediated pathways in regulating cell fates in the zebrafish gastrula. Dev. Biol. 241, 59-78 (2002).
86. Reversade, B. & De Robertis, E. M. Reciprocal regulation of Admp and Bmp2/4/7 at opposite embryonic poles generates a self-regulating morphogenetic field. Cell 123, 1147-1160 (2005).
87. Kimelman, D. & Pyati, U. J. Bmp signaling: turning a half into a whole. Cell 123, 982-984 (2005).
88. Wardle, F. C. & Smith, J. C. Refinement of gene expression patterns in the early Xenopus embryo. Development 131, 4687-4696 (2004).
89. Grimm, O. H. & Gurdon, J. B. Nuclear exclusion of Smad2 is a mechanism leading to loss of competence. Nature Cell Biol. 4, 519-522 (2002).
90. Mohammadi, M. et al. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 276, 955-960 (1997).
91. DaCosta Byfield, S., Major, C., Laping, N. J. & Roberts, A. B. SB-505124 is a selective inhibitor of transforming growth factor β type I receptors ALK4, ALK5, and ALK7. Mol Pharmacol 65, 744-752 (2004).
92. Delaune, E., Lemaire, P. & Kodjabachian, L. Neural induction in Xenopus requires early FGF signalling in addition to BMP inhibition. Development 132, 299-310 (2005).
93. Galli, A., Roure, A., Zeller, R. & Dono, R. Glypican 4 modulates FGF signalling and regulates dorsoventral forebrain patterning in Xenopus embryos. Development 130, 4919-4929 (2003).
94. Jackman, W. R., Draper, B. W. & Stock, D. W. Fgf signaling is required for zebrafish tooth development. Dev. Biol. 274, 139-157 (2004).
95. Pyati, U. J., Webb, A. E. & Kimelman, D. Transgenic zebrafish reveal stage-specific roles for Bmp signaling in ventral and posterior mesoderm development. Development 132, 2333-2343 (2005).
96. Lewis, J. L. et al. Reiterated Wnt signaling during zebrafish neural crest development. Development 131, 1299-1308 (2004).
97. Sivak, J. M., Petersen, L. F. & Amaya, E. FGF signal interpretation is directed by Sprouty and Spred proteins during mesoderm formation. Dev. Cell 8, 689-701 (2005).
98. Nishita, M. et al. Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer. Nature 403, 781-785 (2000).
99. Kroll, K. L. & Amaya, E. Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation. Development 122, 3173-3183 (1996).
100. Messenger, N. J. et al. Functional specificity of the Xenopus T-domain protein Brachyury is conferred by its ability to interact with Smad 1. Dev. Cell 8, 599-610 (2005).
101. Skromne, I. & Stern, C. D. A hierarchy of gene expression accompanying induction of the primitive streak by Vg1 in the chick embryo. Mech. Dev. 114, 115-118 (2002).
102. Bertocchini, F. & Stern, C. D. The hypoblast of the chick embryo positions the primitive streak by antagonizing nodal signaling. Dev. Cell 3, 735-744 (2002).
103. Bertocchini, F., Skromne, I., Wolpert, L. & Stern, C. D. Determination of embryonic polarity in a regulative system: evidence for endogenous inhibitors acting sequentially during primitive streak formation in the chick embryo. Development 131, 3381-3390 (2004).
104. Tam, P. P. L. & Gad, J. M. in Gastrulation (ed. Stern, C. D.) 233-262 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004).
105. Rivera-Perez, J. A. & Magnuson, T. Primitive streak formation in mice is preceded by localized activation of Brachyury and Wnt3. Dev. Biol. 288, 363-371 (2005).
106. Liu, P. et al. Requirement for Wnt3 in vertebrate axis formation. Nature Genet. 22, 361-365 (1999).
107. Yamamoto, M. et al. Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo. Nature 428, 387-392 (2004).
108. Perea-Gomez, A. et al. Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Dev. Cell 3, 745-756 (2002).
109. Kemp, C., Willems, E., Abdo, S., Lambiv, L. & Leyns, L. Expression of all Wnt genes and their secreted antagonists during mouse blastocyst and postimplantation development. Dev. Dyn. 233, 1064-1075 (2005).
110. Mishina, Y., Suzuki, A., Ueno, N. & Behringer, R. R. Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes Dev. 9, 3027-3037 (1995).
111. Winnier, G., Blessing, M., Labosky, P. A. & Hogan, B. L. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 9, 2105-2116 (1995).
112. Taverner, N. V. et al. Microarray-based identification of VegT targets in Xenopus. Mech. Dev. 122, 333-354 (2005).
113. Chung, H. A. et al. Screening of FGF target genes in Xenopus by microarray: temporal dissection of the signalling pathway using a chemical inhibitor. Genes Cells 9, 749-761 (2004).
114. Okabayashi, K. & Asashima, M. Tissue generation from amphibian animal caps. Curr. Opin. Genet. Dev. 13, 502-507 (2003).
115. Fukui, Y. et al. Long-term culture of Xenopus presumptive ectoderm in a nutrient-supplemented culture medium. Dev. Growth Differ. 45, 499-506 (2003).
116. Amaya, E. Xenomics. Genome Res. 15, 1683-1691 (2005).
117. Chen, J. A., Voigt, J., Gilchrist, M., Papalopulu, N. & Amaya, E. Identification of novel genes affecting mesoderm formation and morphogenesis through an enhanced large scale functional screen in Xenopus. Mech. Dev. 122, 307-331 (2005).
118. Loose, M. & Patient, R. A genetic regulatory network tor Xenopus mesendoderm formation. Dev. Biol. 271, 467-478 (2004).
119. Feng, X. H. & Derynck, R. Specificity and versatility in TGF-β signaling through Smads. Annu. Rev. Cell Dev. Biol. 21, 659-693 (2005).
120. van Es, J. H., Barker, N. & Clevers, H. You Wnt some, you lose some: oncogenes in the Wnt signaling pathway. Curr. Opin. Genet. Dev. 13, 28-33 (2003).
121. Thisse, B. & Thisse, C. Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev. Biol. 287, 390-402 (2005).
122. Shen, M. M. & Schier, A. F. The EGF-CFC gene family in vertebrate development. Trends Genet. 16, 303-309 (2000).
123. Dorey, K. & Hill, C. S. A novel Cripto-related protein reveals an essential role for EGF-CFCs in Nodal signalling in Xenopus embryos. Dev. Biol. 20 February 2006 (doi:10.1016/j.ydbio.2006.01.006).
124. Cheng, S. K., Olale, F., Bennett, J. T., Brivanlou, A. H. & Schier, A. F. EGF-CFC proteins are essential coreceptors for the TGF-β signals Vg1 and GDF1. Genes Dev. 17, 31-36 (2003).
125. Lane, M. C., Davidson, L. & Sheets, M. D. BMP antagonism by Spemann's organizer regulates rostral-caudal fate of mesoderm. Dev. Biol. 275, 356-374 (2004).
126. Lieschke, G. J. et al. Zebrafish SPI-1 (PU.1) marks a site of myeloid development independent of primitive erythropoiesis: implications for axial patterning. Dev. Biol. 246, 274-295 (2002).