Response to nodal morphogen gradient is determined by the kinetics of target gene induction

eLife

Volumn 2015, Issue 4, 2015, Pages

  Dubrulle, Julien ^a   Jordan, Benjamin M ^a,b   Akhmetova, Laila ^a   Farrell, Jeffrey A ^a   Kim, Seok Hyung ^c   Solnica Krezel, Lilianna ^d,e   Schier, Alexander F ^a,f,g  

^a HARVARD UNIVERSITY   (United States)

^b University of Minnesota   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^d WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^f HARVARD STEM CELL INSTITUTE   (United States)

^g BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOHEXIMIDE; ETHYLNITROSOUREA; GOOSECOID PROTEIN; HEPATOCYTE NUCLEAR FACTOR 3GAMMA; HISTONE H2B; MESSENGER RNA; MORPHOGEN; NODAL SIGNALING PROTEIN; SMAD2 PROTEIN; GREEN FLUORESCENT PROTEIN; PROTEIN NODAL;

ARTICLE; CHROMATIN IMMUNOPRECIPITATION; EMBRYO; GENE EXPRESSION; GENE INDUCTION; GENETIC TRANSCRIPTION; IN SITU HYBRIDIZATION; KINETICS; MUTANT; NONHUMAN; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA EXTRACTION; SPATIOTEMPORAL ANALYSIS; TIME LAPSE IMAGING; WESTERN BLOTTING; ZEBRA FISH; ANIMAL; BIOLOGICAL MODEL; DRUG EFFECTS; EMBRYOLOGY; ENDODERM; FEMALE; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MORPHOGENESIS; MOUSE; SIGNAL TRANSDUCTION; TIME; TRANSCRIPTION INITIATION; TRANSGENE;

DANIO RERIO;

ANIMALS; BODY PATTERNING; ENDODERM; FEMALE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GREEN FLUORESCENT PROTEINS; KINETICS; MICE; MODELS, BIOLOGICAL; NODAL PROTEIN; SIGNAL TRANSDUCTION; SMAD2 PROTEIN; TIME FACTORS; TRANSCRIPTION, GENETIC; TRANSCRIPTIONAL ACTIVATION; TRANSGENES; ZEBRAFISH;

EID: 85027074381     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/elife.05042     Document Type: Article

References (106)

1. Ashe HL, Briscoe J. 2006. The interpretation of morphogen gradients. Development 133:385–394. doi: 10.1242/dev.02238.
2. Balaskas N, Ribeiro A, Panovska J, Dessaud E, Sasai N, Page KM, Briscoe J, Ribes V. 2012. Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube. Cell 148:273–284. doi: 10.1016/j.cell.2011.10.047.
3. Barkai N, Shilo BZ. 2009. Robust generation and decoding of morphogen gradients. Cold Spring Harbor Perspectives in Biology 1:a001990. doi: 10.1101/cshperspect.a001990.
4. Bennett JT, Joubin K, Cheng S, Aanstad P, Herwig R, Clark M, Lehrach H, Schier AF. 2007. Nodal signaling activates differentiation genes during zebrafish gastrulation. Developmental Biology 304:525–540. doi: 10.1016/j.ydbio.2007.01.012.
5. Bialek W. 2012. Biophysics: searching for principles. Princeton University Press.
6. Bolouri H, Davidson EH. 2003. Transcriptional regulatory cascades in development: initial rates, not steady state, determine network kinetics. Proceedings of the National Academy of Sciences of USA 100:9371–9376. doi: 10.1073/pnas.1533293100.
7. Bourillot PY, Garrett N, Gurdon JB. 2002. A changing morphogen gradient is interpreted by continuous transduction flow. Development 129:2167–2180.
8. Briscoe J, Ericson J. 1999. The specification of neuronal identity by graded Sonic Hedgehog signalling. Seminars in Cell & Developmental Biology 10:353–362. doi: 10.1006/scdb.1999.0295.
9. Burz DS, Rivera-Pomar R, Jäckle H, Hanes SD. 1998. Cooperative DNA-binding by Bicoid provides a mechanism for threshold-dependent gene activation in the Drosophila embryo. The EMBO Journal 17:5998–6009. doi: 10.1093/emboj/17.20.5998.
10. Chen AE, Borowiak M, Sherwood RI, Kweudjeu A, Melton DA. 2013. Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation. Development 140:675–686. doi: 10.1242/dev.085431.
11. Chen H, Xu Z, Mei C, Yu D, Small S. 2012. A system of repressor gradients spatially organizes the boundaries of Bicoid-dependent target genes. Cell 149:618–629. doi: 10.1016/j.cell.2012.03.018.
12. Chen Y, Schier AF. 2001. The zebrafish Nodal signal Squint functions as a morphogen. Nature 411:607–610. doi: 10.1038/35079121.
13. Chen WW, Niepel M, Sorger PK. 2010. Classic and contemporary approaches to modeling biochemical reactions. Genes & Development 24:1861–1875. doi: 10.1101/gad.1945410.
14. Cheng SK, Olale F, Bennett JT, Brivanlou AH, Schier AF. 2003. EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1. Genes & Development 17:31–36. doi: 10.1101/gad.1041203.
15. Ciruna B, Weidinger G, Knaut H, Thisse B, Thisse C, Raz E, Schier AF. 2002. Production of maternal-zygotic mutant zebrafish by germ-line replacement. Proceedings of the National Academy of Sciences of USA 99:14919–14924. doi: 10.1073/pnas.222459999.
16. Clarke DC, Betterton MD, Liu X. 2006. Systems theory of Smad signalling. Systems Biology 153:412–424. doi: 10.1049/ip-syb:20050055.
17. Cohen M, Briscoe J, Blassberg R. 2013. Morphogen interpretation: the transcriptional logic of neural tube patterning. Current opinion in Genetics & Development 23:423–428. doi: 10.1016/j.gde.2013.04.003.
18. Coulon A, Chow CC, Singer RH, Larson DR. 2013. Eukaryotic transcriptional dynamics: from single molecules to cell populations. Nature Reviews Genetics 14:572–584. doi: 10.1038/nrg3484.
19. Conlon FL, Lyons KM, Takaesu N, Barth KS, Kispert A, Herrmann B, Robertson EJ. 1994. A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development 120:1919–1928.
20. Dessaud E, Yang LL, Hill K, Cox B, Ulloa F, Ribeiro A, Mynett A, Novitch BG, Briscoe J. 2007. Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism. Nature 450:717–720. doi: 10.1038/nature06347.
21. Dick A, Mayr T, Bauer H, Meier A, Hammerschmidt M. 2000. Cloning and characterization of zebrafish smad2, smad3 and smad4. Gene 246:69–80. doi: 10.1016/S0378-1119(00)00056-1.
22. Dougan ST, Warga RM, Kane DA, Schier AF, Talbot WS. 2003. The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm. Development 130:1837–1851. doi: 10.1242/dev.00400.
23. Driever W, Nüsslein-Volhard C. 1988. A gradient of bicoid protein in Drosophila embryos. Cell 54:83–93. doi: 10.1016/0092-8674(88)90182-1.
24. Driever W, Thoma G, Nüsslein-Volhard C. 1989. Determination of spatial domains of zygotic gene expression in the Drosophila embryo by the affinity of binding sites for the bicoid morphogen. Nature 340:363–367. doi: 10.1038/340363a0.
25. Duboc V, Lapraz F, Saudemont A, Bessodes N, Mekpoh F, Haillot E, Quirin M, Lepage T. 2010. Nodal and BMP2/4 pattern the mesoderm and endoderm during development of the sea urchin embryo. Development 137: 223–235. doi: 10.1242/dev.042531.
26. Dyson S, Gurdon JB. 1998. The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors. Cell 93:557–568. doi: 10.1016/S0092-8674(00)81185-X.
27. Faure S, Lee MA, Keller T, ten Dijke P, Whitman M. 2000. Endogenous patterns of TGFbeta superfamily signaling during early Xenopus development. Development 127:2917–2931.
28. Feldman B, Dougan ST, Schier AF, Talbot WS. 2000. Nodal-related signals establish mesendodermal fate and trunk neural identity in zebrafish. Current Biology 10:531–534. doi: 10.1016/S0960-9822(00)00469-3.
29. Feldman B, Gates MA, Egan ES, Dougan ST, Rennebeck G, Sirotkin HI, Schier AF, Talbot WS. 1998. Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature 395:181–185. doi: 10.1038/26013.
30. Feldman B, Stemple DL. 2001. Morpholino phenocopies of sqt, oep, and ntl mutations. Genesis 30:175–177. doi: 10.1002/gene.1058.
31. Fodor E, Zsigmond Á, Horváth B, Molnár J, Nagy I, Tóth G, Wilson SW, Varga M. 2013. Full transcriptome analysis of early dorsoventral patterning in zebrafish. PLOS ONE 8:e70053. doi: 10.1371/journal.pone.0070053.
32. Foo SM, Sun Y, Lim B, Ziukaite R, O’Brien K, Nien CY, Kirov N, Shvartsman SY, Rushlow CA. 2014. Zelda potentiates morphogen activity by increasing chromatin accessibility. Current Biology 24:1341–1346. doi: 10.1016/j.cub.2014.04.032.
33. Geertz M, Shore D, Maerkl SJ. 2012. Massively parallel measurements of molecular interaction kinetics on a microfluidic platform. Proceedings of the National Academy of Sciences of USA 109:16540–16545. doi: 10.1073/pnas.1206011109.
34. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, Fell HP, Ferree S, George RD, Grogan T, James JJ, Maysuria M, Mitton JD, Oliveri P, Osborn JL, Peng T, Ratcliffe AL, Webster PJ, Davidson EH, Hood L, Dimitrov K. 2008. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nature biotechnology 26:317–325. doi: 10.1038/nbt1385.
35. Gentsch GE, Owens NDL, Martin SR, Piccinelli P, Faial T, Trotter MWB, Gilchrist MJ, Smith JC. 2013. In vivo T-box transcription factor profiling reveals joint regulation of embryonic neuromesodermal bipotency. Cell Reports 4: 1185–1196. doi: 10.1016/j.celrep.2013.08.012.
36. Grande C, Patel NH. 2009. Nodal signalling is involved in left-right asymmetry in snails. Nature 457:1007–1011. doi: 10.1038/nature07603.
37. Gregor T, Wieschaus EF, McGregor AP, Bialek W, Tank DW. 2007. Stability and nuclear dynamics of the bicoid morphogen gradient. Cell 130:141–152. doi: 10.1016/j.cell.2007.05.026.
38. Gritsman K, Talbot WS, Schier AF. 2000. Nodal signaling patterns the organizer. Development 127:921–932.
39. Gritsman K, Zhang J, Cheng S, Heckscher E, Talbot WS, Schier AF. 1999. The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell 97:121–132. doi: 10.1016/S0092-8674(00)80720-5.
40. Gurdon JB, Dyson S, St Johnston D. 1998. Cells’ perception of position in a concentration gradient. Cell 95: 159–162. doi: 10.1016/S0092-8674(00)81747-X.
41. Gurdon JB, Mitchell A, Mahony D. 1995. Direct and continuous assessment by cells of their position in a morphogen gradient. Nature 376:520–521. doi: 10.1038/376520a0.
42. Guzman-Ayala M, Lee KL, Mavrakis KJ, Goggolidou P, Norris DP, Episkopou V. 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.
43. Hager GL, McNally JG, Misteli T. 2009. Transcription dynamics. Molecular Cell 35:741–753. doi: 10.1016/j.molcel.2009.09.005.
44. Hagos EG, Dougan ST. 2007. Time-dependent patterning of the mesoderm and endoderm by Nodal signals in zebrafish. BMC Developmental Biology 7:22. doi: 10.1186/1471-213X-7-22.
45. Harvey SA, Smith JC. 2009. Visualisation and quantification of morphogen gradient formation in the zebrafish. PLOS Biology 7:e1000101. doi: 10.1371/journal.pbio.1000101.
46. Inman GJ, Nicolá s FJ, Hill CS. 2002. Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity. Molecular Cell 10:283–294. doi: 10.1016/S1097-2765(02)00585-3.
47. 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. doi: 10.1242/dev.01706.
48. Jia S, Ren Z, Li X, Zheng Y, Meng A. 2008. smad2 and smad3 are required for mesendoderm induction by transforming growth factor-beta/nodal signals in zebrafish. The Journal of Biological Chemistry 283:2418–2426. doi: 10.1074/jbc.M707578200.
49. Jullien J, Gurdon J. 2005. Morphogen gradient interpretation by a regulated trafficking step during ligandreceptor transduction. Genes & Development 19:2682–2694. doi: 10.1101/gad.341605.
50. Kanodia JS, Liang H-L, Kim Y, Lim B, Zhan M, Lu H, Rushlow CA, Shvartsman SY. 2012. Pattern formation by graded and uniform signals in the early Drosophila embryo. Biophysical Journal 102:427–433. doi: 10.1016/j.bpj.2011.12.042.
51. Karlen S, Rebagliati M. 2001. A morpholino phenocopy of the cyclops mutation. Genesis 30:126–128. doi: 10.1002/gene.1046.
52. Kulkarni MM. 2011. Digital multiplexed gene expression analysis using the NanoString nCounter system. Current Protocols in Molecular Biology, Chapter 25, Unit25B.10. doi: 10.1002/0471142727.mb25b10s94.
53. de-Leon SB, Davidson EH. 2010. Information processing at the foxa node of the sea urchin endomesoderm specification network. Proceedings of the National Academy of Sciences of USA 107:10103–10108. doi: 10.1073/pnas.1004824107.
54. Lewis J. 2003. Autoinhibition with transcriptional delay: a simple mechanism for the zebrafish somitogenesis oscillator. Current Biology 13:1398–1408. doi: 10.1016/S0960-9822(03)00534-7.
55. Li B, Carey M, Workman JL. 2007. The role of chromatin during transcription. Cell 128:707–719. doi: 10.1016/j.cell.2007.01.015.
56. Liu Z, Lin X, Cai Z, Zhang Z, Han C, Jia S, Meng A, Wang Q. 2011. Global identification of SMAD2 target genes reveals a role for multiple co-regulatory factors in zebrafish early gastrulas. The Journal of Biological Chemistry 286:28520–28532. doi: 10.1074/jbc.M111.236307.
57. Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS, Brown M. 2008. FoxA1 translates epigenetic signatures into enhancer driven lineage-specific transcription. Cell 132:958–970. doi: 10.1016/j.cell.2008.01.018.
58. Martin BL, Kimelman D. 2008. Regulation of canonical Wnt signaling by Brachyury is essential for posterior mesoderm formation. Developmental Cell 15:121–133. doi: 10.1016/j.devcel.2008.04.013.
59. Massagué J. 2012. TGFβ signalling in context. Nature ReviewsMolecular Cell Biology 13:616–630. doi: 10.1038/nrm3434.
60. Miller C, Schwalb B, Maier K, Schulz D, Dümcke S, Zacher B, Mayer A, Sydow J, Marcinowski L, Dölken L, Martin DE, Tresch A, Cramer P. 2011. Dynamic transcriptome analysis measures rates of mRNA synthesis and decay in yeast. Molecular Systems Biology 7:458. doi: 10.1038/msb.2010.112.
61. Müller P, Rogers KW, Jordan BM, Lee JS, Robson D, Ramanathan S, Schier AF. 2012. Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system. Science 336:721–724. doi: 10.1126/science.1221920.
62. Müller P, Rogers KW, Yu SR, Brand M, Schier AF. 2013. Morphogen transport. Development 140:1621–1638. doi: 10.1242/dev.083519.
63. Nam J, Davidson EH. 2012. Barcoded DNA-tag reporters for multiplex cis-regulatory analysis. PLOS ONE 7: e35934. doi: 10.1371/journal.pone.0035934.
64. Nicolá s FJ, De Bosscher K, Schmierer B, Hill CS. 2004. Analysis of Smad nucleocytoplasmic shuttling in living cells. Journal of Cell Science 117:4113–4125. doi: 10.1242/jcs.01289.
65. Nishi Y, Ji H, Wong WH, McMahon AP, Vokes SA. 2009. Modeling the spatio-temporal network that drives patterning in the vertebrate central nervous system. Biochimica Et Biophysica Acta 1789:299–305. doi: 10.1016/j.bbagrm.2009.01.002.
66. Oates AC, Morelli LG, Ares S. 2012. Patterning embryos with oscillations: structure, function and dynamics of the vertebrate segmentation clock. Development 139:625–639. doi: 10.1242/dev.063735.
67. Ochoa-Espinosa A, Yu D, Tsirigos A, Struffi P, Small S. 2009. Anterior-posterior positional information in the absence of a strong Bicoid gradient. Proceedings of the National Academy of Sciences of USA 106:3823–3828. doi: 10.1073/pnas.0807878105.
68. Oosterveen T, Kurdija S, Ensterö M, Uhde CW, Bergsland M, Sandberg M, Sandberg R, Muhr J, Ericson J. 2013. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals. Proceedings of the National Academy of Sciences of USA 110:7330–7335. doi: 10.1073/pnas.1220010110.
69. Oshimori N, Fuchs E. 2012. The Harmonies Played by TGF-? in stem cell biology. Cell Stem Cell 11:751–764. doi: 10.1016/j.stem.2012.11.001.
70. Peterson KA, Nishi Y, Ma W, Vedenko A, Shokri L, Zhang X, McFarlane M, Baizabal JM, Junker JP, van Oudenaarden A, Mikkelsen T, Bernstein BE, Bailey TL, Bulyk ML, Wong WH, McMahon AP. 2012. Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning. Genes & Development 26:2802–2816. doi: 10.1101/gad.207142.112.
71. Porcher A, Abu-Arish A, Huart S, Roelens B, Fradin C, Dostatni N. 2010. The time to measure positional information: maternal hunchback is required for the synchrony of the Bicoid transcriptional response at the onset of zygotic transcription. Development 137:2795–2804. doi: 10.1242/dev.051300.
72. Rabani M, Levin JZ, Fan L, Adiconis X, Raychowdhury R, Garber M, Gnirke A, Nusbaum C, Hacohen N, Friedman N, Amit I, Regev A. 2011. Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells. Nature Biotechnology 29:436–442. doi: 10.1038/nbt.1861.
73. Rogers KW, Schier AF. 2011. Morphogen gradients: from generation to interpretation. Annual Review of Cell and Developmental Biology 27:377–407. doi: 10.1146/annurev-cellbio-092910-154148.
74. Sampath K, Rubinstein AL, Cheng AM, Liang JO, Fekany K, Solnica-Krezel L, Korzh V, Halpern ME, Wright CV. 1998. Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling. Nature 395: 185–189. doi: 10.1038/26020.
75. Satija R, Farrell JA, Gennert D, Schier AF, Regev A. Spatial reconstruction of single-cell gene expression. Nature Biotechnology. doi: 10.1038/nbt.3192.
76. Schier AF. 2009. Nodal morphogens. Cold Spring Harbor Perspectives in Biology 1:a003459. doi: 10.1101/cshperspect.a003459.
77. Schier AF, Neuhauss SC, Helde KA, Talbot WS, Driever W. 1997. The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. Development 124:327–342.
78. Schmierer B, Hill CS. 2005. Kinetic analysis of Smad nucleocytoplasmic shuttling reveals a mechanism for transforming growth factor beta-dependent nuclear accumulation of Smads. Molecular and Cellular Biology 25: 9845–9858. doi: 10.1128/MCB.25.22.9845-9858.2005.
79. Schmierer B, Tournier AL, Bates PA, Hill CS. 2008. Mathematical modeling identifies Smad nucleocytoplasmic shuttling as a dynamic signal-interpreting system. Proceedings of the National Academy of Sciences of USA 105: 6608–6613. doi: 10.1073/pnas.0710134105.
80. Schulte-Merker S, Hammerschmidt M, Beuchle D, Cho KW, Robertis EM, Nusslein-Volhard C. 1994. Expression of zebrafish goosecoid and no tail gene products in wild-type and mutant no tail embryos. Development 120: 843–852.
81. Schulte-Merker S, Ho RK, Herrmann BG, Nüsslein-Volhard C. 1992. The protein product of the zebrafish homologue of the mouse T gene is expressed in nuclei of the germ ring and the notochord of the early embryo. Development 116:1021–1032.
82. Shen MM. 2007. Nodal signaling: developmental roles and regulation. Development 134:1023–1034. doi: 10.1242/dev.000166.
83. Shiratori H, Hamada H. 2014. TGFβ signaling in establishing left-right asymmetry. Seminars in Cell & Developmental Biology 32:80–84. doi: 10.1016/j.semcdb.2014.03.029.
84. Sorre B, Warmflash A, Brivanlou AH, Siggia ED. 2014. Encoding of temporal signals by the TGF-β pathway and implications for embryonic patterning. Developmental Cell 30:334–342. doi: 10.1016/j.devcel.2014.05.022.
85. Strobl-Mazzulla PH, Sauka-Spengler T, Bronner-Fraser M. 2010. Histone demethylase JmjD2A regulates neural crest specification. Developmental Cell 19:460–468. doi: 10.1016/j.devcel.2010.08.009.
86. Su YH, Li E, Geiss GK, Longabaugh WJ, Krämer A, Davidson EH. 2009. A perturbation model of the gene regulatory network for oral and aboral ectoderm specification in the sea urchin embryo. Developmental Biology 329:410–421. doi: 10.1016/j.ydbio.2009.02.029.
87. ten Dijke P, Hill CS. 2004. New insights into TGF-beta-Smad signalling. Trends in Biochemical Sciences 29: 265–273. doi: 10.1016/j.tibs.2004.03.008.
88. Thermes V, Grabher C, Ristoratore F, Bourrat F, Choulika A, Wittbrodt J, Joly JS. 2002. I-SceI meganuclease mediates highly efficient transgenesis in fish. Mechanisms of Development 118:91–98. doi: 10.1016/S0925-4773(02)00218-6.
89. Thisse B, Wright CV, Thisse C. 2000. Activin- and Nodal-related factors control antero–posterior patterning of the zebrafish embryo. Nature 403:425–428. doi: 10.1038/35000200.
90. Tu Q, Cameron RA, Davidson EH. 2014. Quantitative developmental transcriptomes of the sea urchin Strongylocentrotus purpuratus. Developmental Biology 385:160–167. doi: 10.1016/j.ydbio.2013.11.019.
91. Vallier L, Alexander M, Pedersen RA. 2005. Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells. Journal of Cell Science 118:4495–4509. doi: 10.1242/jcs.02553.
92. Vizán P, Miller DSJ, Gori I, Das D, Schmierer B, Hill CS. 2013. Controlling long-term signaling: receptor dynamics determine attenuation and refractory behavior of the TGF-β pathway. Science Signaling 6:ra106. doi: 10.1126/scisignal.2004416.
93. Wienholds E, van Eeden F, Kosters M, Mudde J, Plasterk RHA, Cuppen E. 2003. Efficient target-selected mutagenesis in zebrafish. Genome Research 13:2700–2707. doi: 10.1101/gr.1725103.
94. Williams PH, Hagemann A, González-Gaitán M, Smith JC. 2004. Visualizing long-range movement of the morphogen Xnr2 in the Xenopus embryo. Current Biology 14:1916–1923. doi: 10.1016/j.cub.2004.10.020.
95. Xi Q, Wang Z, Zaromytidou A-I, Zhang XH, Chow-Tsang LF, Liu JX, Kim H, Barlas A, Manova-Todorova K, Kaartinen V, Studer L, Mark W, Patel DJ, Massagué J. 2011. A poised chromatin platform for TGF-β access to master regulators. Cell 147:1511–1524. doi: 10.1016/j.cell.2011.11.032.
96. Xiong F, Tentner AR, Huang P, Gelas A, Mosaliganti KR, Souhait L, Rannou N, Swinburne IA, Obholzer ND, Cowgill PD, Schier AF, Megason SG. 2013. Specified neural progenitors Sort to form Sharp domains after noisy shh signaling. Cell 153:550–561. doi: 10.1016/j.cell.2013.03.023.
97. Xu L, Kang Y, Çöl S, Massagué J. 2002. Smad2 nucleocytoplasmic shuttling by Nucleoporins CAN/Nup214 and Nup153 Feeds TGFβ signaling complexes in the Cytoplasm and nucleus. Molecular Cell 10:271–282. doi: 10.1016/S1097-2765(02)00586-5.
98. Xu L, Massagué J. 2004. Nucleocytoplasmic shuttling of signal transducers. Nature Reviews Molecular Cell Biology 5:209–219. doi: 10.1038/nrm1331.
99. Xu PF, Houssin N, Ferri-Lagneau KF, Thisse B, Thisse C. 2014a. Construction of a vertebrate embryo from two opposing morphogen gradients. Science 344:87–89. doi: 10.1126/science.1248252.
100. Xu Z, Chen H, Ling J, Yu D, Struffi P, Small S. 2014b. Impacts of the ubiquitous factor Zelda on Bicoid-dependent DNA binding and transcription in Drosophila. Genes & Development 28:608–621. doi: 10.1101/gad.234534.113.
101. Yeo C, Whitman M. 2001. Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Molecular Cell 7:949–957. doi: 10.1016/S1097-2765(01)00249-0.
102. Yoon SJ, Wills AE, Chuong E, Gupta R, Baker JC. 2011. HEB and E2A function as SMAD/FOXH1 cofactors. Genes & Development 25:1654–1661. doi: 10.1101/gad.16800511.
103. Zhang J, Talbot WS, Schier AF. 1998. Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGFrelated ligand required during gastrulation. Cell 92:241–251. doi: 10.1016/S0092-8674(00)80918-6.
104. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nusbaum C, Myers RM, Brown M, Li W, Liu XS. 2008. Model-based analysis of ChIP-Seq (MACS). Genome Biology 9:R137. doi: 10.1186/gb-2008-9-9-r137.
105. Zi Z, Feng Z, Chapnick DA, Dahl M, Deng D, Klipp E, Moustakas A, Liu X. 2011. Quantitative analysis of transient and sustained transforming growth factor-β signaling dynamics. Molecular Systems Biology 7:492. doi: 10.1038/msb.2011.22.
106. Zi Z, Klipp E. 2007. Constraint-based modeling and kinetic analysis of the smad dependent TGF-β signaling pathway. PLOS ONE 2:e936. doi: 10.1371/journal.pone.0000936.