Graded Nodal/Activin signaling titrates conversion of quantitative phospho-Smad2 levels into qualitative embryonic stem cell fate decisions

PLoS Genetics

Volumn 7, Issue 6, 2011, Pages

  Lee, Kian Leong ^a,b   Lim, Sandy Keat ^b,c,d   Orlov, Yuriy Lvovich ^b,e   Yit, Le Yau ^a   Yang, Henry ^f   Ang, Lay Teng ^b   Poellinger, Lorenz ^a,g   Lim, Bing ^b,h  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b GENOME INSTITUTE OF SINGAPORE   (Singapore)

^c NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^d NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^e INSTITUTE OF CYTOLOGY AND GENETICS   (Russian Federation)

^f AGENCY FOR SCIENCE   (Singapore)

^g KAROLINSKA INSTITUTE   (Sweden)

^h HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN; OCTAMER TRANSCRIPTION FACTOR 4; PROTEIN NODAL; SMAD2 PROTEIN; 1,3 DIOXOLANE DERIVATIVE; 4 (5 BENZO(1,3)DIOXOL 5 YL 4 PYRIDIN 2 YL 1H IMIDAZOL 2 YL)BENZAMIDE; 4-(5-BENZO(1,3)DIOXOL-5-YL-4-PYRIDIN-2-YL-1H-IMIDAZOL-2-YL)BENZAMIDE; ACTIVIN RECEPTOR; BENZAMIDE DERIVATIVE; DIMETHYL SULFOXIDE; NODAL PROTEIN, MOUSE; POU5F1 PROTEIN, MOUSE; SMAD2 PROTEIN, MOUSE;

ANIMAL CELL; ARTICLE; CELL FATE; CELL RENEWAL; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; EMBRYO; EMBRYO DEVELOPMENT; EMBRYONIC STEM CELL; GENE CONTROL; GENE TARGETING; MOUSE; NONHUMAN; PROMOTER REGION; PROTEIN DNA BINDING; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; ANIMAL; CELL CULTURE; CELL DIFFERENTIATION; CYTOLOGY; DNA MICROARRAY; DRUG ANTAGONISM; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; GERM LAYER; METABOLISM; PHOSPHORYLATION; PROTEIN BINDING;

ACTIVIN RECEPTORS; ACTIVINS; ANIMALS; BENZAMIDES; CELL DIFFERENTIATION; CELLS, CULTURED; DIMETHYL SULFOXIDE; DIOXOLES; EMBRYONIC STEM CELLS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GERM LAYERS; MICE; NODAL PROTEIN; OCTAMER TRANSCRIPTION FACTOR-3; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; SIGNAL TRANSDUCTION; SMAD2 PROTEIN; TRANSCRIPTIONAL ACTIVATION;

EID: 79959814756     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1002130     Document Type: Article

References (67)

1. Ashe HL, Briscoe J, (2006) The interpretation of morphogen gradients. Development 133: 385-394.
2. Gurdon JB, Bourillot PY, (2001) Morphogen gradient interpretation. Nature 413: 797-803.
3. Tabata T, Takei Y, (2004) Morphogens, their identification and regulation. Development 131: 703-712.
4. Green JB, Smith JC, (1990) Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate. Nature 347: 391-394.
5. Gurdon JB, Harger P, Mitchell A, Lemaire P, (1994) Activin signalling and response to a morphogen gradient. Nature 371: 487-492.
6. Chen Y, Schier AF, (2001) The zebrafish Nodal signal Squint functions as a morphogen. Nature 411: 607-610.
7. Perea-Gomez A, Vella FD, Shawlot W, Oulad-Abdelghani M, Chazaud C, et al. (2002) Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Dev Cell 3: 745-756.
8. Mavrakis KJ, Andrew RL, Lee KL, Petropoulou C, Dixon JE, et al. (2007) Arkadia enhances Nodal/TGF-beta signaling by coupling phospho-Smad2/3 activity and turnover. PLoS Biol 5: e67 doi:10.1371/journal.pbio.0050067.
9. Vincent SD, Dunn NR, Hayashi S, Norris DP, Robertson EJ, (2003) Cell fate decisions within the mouse organizer are governed by graded Nodal signals. Genes Dev 17: 1646-1662.
10. Conlon FL, Lyons KM, Takaesu N, Barth KS, Kispert A, et al. (1994) A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development 120: 1919-1928.
11. Tremblay KD, Hoodless PA, Bikoff EK, Robertson EJ, (2000) Formation of the definitive endoderm in mouse is a Smad2-dependent process. Development 127: 3079-3090.
12. James D, Levine AJ, Besser D, Hemmati-Brivanlou A, (2005) TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132: 1273-1282.
13. Xiao L, Yuan X, Sharkis SJ, (2006) Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells. Stem Cells 24: 1476-1486.
14. Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, et al. (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448: 191-195.
15. Beattie GM, Lopez AD, Bucay N, Hinton A, Firpo MT, et al. (2005) Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers. Stem Cells 23: 489-495.
16. Whitman M, Raftery L, (2005) TGFbeta signaling at the summit. Development 132: 4205-4210.
17. Reissmann E, Jornvall H, Blokzijl A, Andersson O, Chang C, et al. (2001) The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development. Genes Dev 15: 2010-2022.
18. Kelber JA, Shani G, Booker EC, Vale WW, Gray PC, (2008) Cripto is a noncompetitive activin antagonist that forms analogous signaling complexes with activin and nodal. J Biol Chem 283: 4490-4500.
19. Kumar A, Novoselov V, Celeste AJ, Wolfman NM, Ten Dijke P, et al. (2001) Nodal signaling uses activin and transforming growth factor-beta receptor-regulated Smads. J Biol Chem 276: 656-661.
20. Moustakas A, Souchelnytskyi S, Heldin CH, (2001) Smad regulation in TGF-beta signal transduction. J Cell Sci 114: 4359-4369.
21. Funaba M, Zimmerman CM, Mathews LS, (2002) Modulation of Smad2-mediated signaling by extracellular signal-regulated kinase. J Biol Chem 277: 41361-41368.
22. Kretzschmar M, Doody J, Timokhina I, Massague J, (1999) A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras. Genes Dev 13: 804-816.
23. Wicks SJ, Lui S, Abdel-Wahab N, Mason RM, Chantry A, (2000) Inactivation of smad-transforming growth factor beta signaling by Ca(2+)-calmodulin-dependent protein kinase II. Mol Cell Biol 20: 8103-8111.
24. Abdollah S, Macias-Silva M, Tsukazaki T, Hayashi H, Attisano L, et al. (1997) TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling. J Biol Chem 272: 27678-27685.
25. Souchelnytskyi S, Tamaki K, Engstrom U, Wernstedt C, Ten Dijke P, et al. (1997) Phosphorylation of Ser465 and Ser467 in the C terminus of Smad2 mediates interaction with Smad4 and is required for transforming growth factor-beta signaling. J Biol Chem 272: 28107-28115.
26. Shi Y, Massague J, (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113: 685-700.
27. Dennler S, Huet S, Gauthier JM, (1999) A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3. Oncogene 18: 1643-1648.
28. Dunn NR, Koonce CH, Anderson DC, Islam A, Bikoff EK, et al. (2005) Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile. Genes Dev 19: 152-163.
29. Nomura M, Li E, (1998) Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature 393: 786-790.
30. Zhu Y, Richardson JA, Parada LF, Graff JM, (1998) Smad3 mutant mice develop metastatic colorectal cancer. Cell 94: 703-714.
31. Koinuma D, Tsutsumi S, Kamimura N, Taniguchi H, Miyazawa K, et al. (2009) Chromatin immunoprecipitation on microarray analysis of Smad2/3 binding sites reveals roles of ETS1 and TFAP2A in transforming growth factor beta signaling. Mol Cell Biol 29: 172-186.
32. Hamada H, Meno C, Watanabe D, Saijoh Y, (2002) Establishment of vertebrate left-right asymmetry. Nat Rev Genet 3: 103-113.
33. Chen C, Shen MM, (2004) Two modes by which Lefty proteins inhibit nodal signaling. Curr Biol 14: 618-624.
34. Hanyu A, Ishidou Y, Ebisawa T, Shimanuki T, Imamura T, et al. (2001) The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling. J Cell Biol 155: 1017-1027.
35. Shiratori H, Sakuma R, Watanabe M, Hashiguchi H, Mochida K, et al. (2001) Two-step regulation of left-right asymmetric expression of Pitx2: initiation by nodal signaling and maintenance by Nkx2. Mol Cell 7: 137-149.
36. Saijoh Y, Adachi H, Mochida K, Ohishi S, Hirao A, et al. (1999) Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2. Genes Dev 13: 259-269.
37. Denissova NG, Pouponnot C, Long J, He D, Liu F, (2000) Transforming growth factor beta-inducible independent binding of SMAD to the Smad7 promoter. Proc Natl Acad Sci U S A 97: 6397-6402.
38. von Gersdorff G, Susztak K, Rezvani F, Bitzer M, Liang D, et al. (2000) Smad3 and Smad4 mediate transcriptional activation of the human Smad7 promoter by transforming growth factor beta. J Biol Chem 275: 11320-11326.
39. Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, et al. (1997) The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell 89: 1165-1173.
40. Inman GJ, Nicolas FJ, Callahan JF, Harling JD, Gaster LM, et al. (2002) SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 62: 65-74.
41. Guzman-Ayala M, Lee KL, Mavrakis KJ, Goggolidou P, Norris DP, et al. (2009) Graded Smad2/3 activation is converted directly into levels of target gene expression in embryonic stem cells. PLoS ONE 4: e4268 doi:10.1371/journal.pone.0004268.
42. Herrmann BG, (1991) Expression pattern of the Brachyury gene in whole-mount TWis/TWis mutant embryos. Development 113: 913-917.
43. Vincentz JW, McWhirter JR, Murre C, Baldini A, Furuta Y, (2005) Fgf15 is required for proper morphogenesis of the mouse cardiac outflow tract. Genesis 41: 192-201.
44. Salgueiro AM, Filipe M, Belo JA, (2006) N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase expression during early mouse embryonic development. Int J Dev Biol 50: 705-708.
45. Ralston A, Cox BJ, Nishioka N, Sasaki H, Chea E,et al. Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2. Development 137: 395-403.
46. Home P, Ray S, Dutta D, Bronshteyn I, Larson M, et al. (2009) GATA3 is selectively expressed in the trophectoderm of peri-implantation embryo and directly regulates Cdx2 gene expression. J Biol Chem 284: 28729-28737.
47. Shi D, Kellems RE, (1998) Transcription factor AP-2gamma regulates murine adenosine deaminase gene expression during placental development. J Biol Chem 273: 27331-27338.
48. Werling U, Schorle H, (2002) Transcription factor gene AP-2 gamma essential for early murine development. Mol Cell Biol 22: 3149-3156.
49. Constancia M, Angiolini E, Sandovici I, Smith P, Smith R, et al. (2005) Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems. Proc Natl Acad Sci U S A 102: 19219-19224.
50. Constancia M, Hemberger M, Hughes J, Dean W, Ferguson-Smith A, et al. (2002) Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 417: 945-948.
51. Saijoh Y, Adachi H, Sakuma R, Yeo CY, Yashiro K, et al. (2000) Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2. Mol Cell 5: 35-47.
52. Smolen GA, Schott BJ, Stewart RA, Diederichs S, Muir B, et al. (2007) A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors. Genes Dev 21: 2131-2136.
53. Hart AH, Hartley L, Sourris K, Stadler ES, Li R, et al. (2002) Mixl1 is required for axial mesendoderm morphogenesis and patterning in the murine embryo. Development 129: 3597-3608.
54. Niederlander C, Walsh JJ, Episkopou V, Jones CM, (2001) Arkadia enhances nodal-related signalling to induce mesendoderm. Nature 410: 830-834.
55. Adachi H, Saijoh Y, Mochida K, Ohishi S, Hashiguchi H, et al. (1999) Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer. Genes Dev 13: 1589-1600.
56. Norris DP, Robertson EJ, (1999) Asymmetric and node-specific nodal expression patterns are controlled by two distinct cis-acting regulatory elements. Genes Dev 13: 1575-1588.
57. Sun X, Meyers EN, Lewandoski M, Martin GR, (1999) Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo. Genes Dev 13: 1834-1846.
58. Boettger T, Wittler L, Kessel M, (1999) FGF8 functions in the specification of the right body side of the chick. Curr Biol 9: 277-280.
59. Niwa H, Miyazaki J, Smith AG, (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24: 372-376.
60. Niwa H, Toyooka Y, Shimosato D, Strumpf D, Takahashi K, et al. (2005) Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation. Cell 123: 917-929.
61. Xu RH, Sampsell-Barron TL, Gu F, Root S, Peck RM, et al. (2008) NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs. Cell Stem Cell 3: 196-206.
62. Watanabe Y, Itoh S, Goto T, Ohnishi E, Inamitsu M,et al. TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad proteins from active participation in TGF-beta signaling. Mol Cell 37: 123-134.
63. Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K, (1999) Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science 286: 771-774.
64. Pessah M, Marais J, Prunier C, Ferrand N, Lallemand F, et al. (2002) c-Jun associates with the oncoprotein Ski and suppresses Smad2 transcriptional activity. J Biol Chem 277: 29094-29100.
65. Katkov, II, Kim MS, Bajpai R, Altman YS, Mercola M, et al. (2006) Cryopreservation by slow cooling with DMSO diminished production of Oct-4 pluripotency marker in human embryonic stem cells. Cryobiology 53: 194-205.
66. Adler S, Pellizzer C, Paparella M, Hartung T, Bremer S, (2006) The effects of solvents on embryonic stem cell differentiation. Toxicol In Vitro 20: 265-271.
67. Chua SW, Vijayakumar P, Nissom PM, Yam CY, Wong VV, et al. (2006) A novel normalization method for effective removal of systematic variation in microarray data. Nucleic Acids Res 34: e38.