Nodal-Dependent Mesendoderm Specification Requires the Combinatorial Activities of FoxH1 and Eomesodermin

English version České info

Vertebrate mesendoderm specification requires the Nodal signaling pathway and its transcriptional effector FoxH1. However, loss of FoxH1 in several species does not reliably cause the full range of loss-of-Nodal phenotypes, indicating that Nodal signals through additional transcription factors during early development. We investigated the FoxH1-dependent and -independent roles of Nodal signaling during mesendoderm patterning using a novel recessive zebrafish FoxH1 mutation called midway, which produces a C-terminally truncated FoxH1 protein lacking the Smad-interaction domain but retaining DNA–binding capability. Using a combination of gel shift assays, Nodal overexpression experiments, and genetic epistasis analyses, we demonstrate that midway more accurately represents a complete loss of FoxH1-dependent Nodal signaling than the existing zebrafish FoxH1 mutant schmalspur. Maternal-zygotic midway mutants lack notochords, in agreement with FoxH1 loss in other organisms, but retain near wild-type expression of markers of endoderm and various nonaxial mesoderm fates, including paraxial and intermediate mesoderm and blood precursors. We found that the activity of the T-box transcription factor Eomesodermin accounts for specification of these tissues in midway embryos. Inhibition of Eomesodermin in midway mutants severely reduces the specification of these tissues and effectively phenocopies the defects seen upon complete loss of Nodal signaling. Our results indicate that the specific combinations of transcription factors available for signal transduction play critical and separable roles in determining Nodal pathway output during mesendoderm patterning. Our findings also offer novel insights into the co-evolution of the Nodal signaling pathway, the notochord specification program, and the chordate branch of the deuterostome family of animals.

Vyšlo v časopise: Nodal-Dependent Mesendoderm Specification Requires the Combinatorial Activities of FoxH1 and Eomesodermin. PLoS Genet 7(5): e32767. doi:10.1371/journal.pgen.1002072
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002072

Souhrn

Zdroje

1. WengWStempleDL 2003 Nodal signaling and vertebrate germ layer formation. Birth Defects Res C Embryo Today 69 325 332

2. FeldmanBGatesMAEganESDouganSTRennebeckG 1998 Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature 395 181 185

3. GritsmanKZhangJChengSHeckscherETalbotWS 1999 The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell 97 121 132

4. SchierAF 2009 Nodal morphogens. Cold Spring Harb Perspect Biol 1 a003459

5. ShenMM 2007 Nodal signaling: developmental roles and regulation. Development 134 1023 1034

6. ChenXRubockMJWhitmanM 1996 A transcriptional partner for MAD proteins in TGF-beta signalling. Nature 383 691 696

7. WhitmanM 2001 Nodal signaling in early vertebrate embryos: themes and variations. Dev Cell 1 605 617

8. HoodlessPAPyeMChazaudCLabbeEAttisanoL 2001 FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse. Genes Dev 15 1257 1271

9. KofronMPuckHStandleyHWylieCOldR 2004 New roles for FoxH1 in patterning the early embryo. Development 131 5065 5078

10. YamamotoMMenoCSakaiYShiratoriHMochidaK 2001 The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse. Genes Dev 15 1242 1256

11. HowellMInmanGJHillCS 2002 A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3) cooperates with XFast-1 in regulating gastrulation movements. Development 129 2823 2834

12. HammerschmidtMPelegriFMullinsMCKaneDABrandM 1996 Mutations affecting morphogenesis during gastrulation and tail formation in the zebrafish, Danio rerio. Development 123 143 151

13. SchierAFNeuhaussSCHarveyMMalickiJSolnica-KrezelL 1996 Mutations affecting the development of the embryonic zebrafish brain. Development 123 165 178

14. Solnica-KrezelLStempleDLMountcastle-ShahERanginiZNeuhaussSC 1996 Mutations affecting cell fates and cellular rearrangements during gastrulation in zebrafish. Development 123 67 80

15. PogodaHMSolnica-KrezelLDrieverWMeyerD 2000 The zebrafish forkhead transcription factor FoxH1/Fast1 is a modulator of nodal signaling required for organizer formation. Curr Biol 10 1041 1049

16. SirotkinHIGatesMAKellyPDSchierAFTalbotWS 2000 Fast1 is required for the development of dorsal axial structures in zebrafish. Curr Biol 10 1051 1054

17. PeiWNoushmehrHCostaJOuspenskaiaMVElkahlounAG 2007 An early requirement for maternal FoxH1 during zebrafish gastrulation. Dev Biol 310 10 22

18. KunwarPSZimmermanSBennettJTChenYWhitmanM 2003 Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction. Development 130 5589 5599

19. LongSAhmadNRebagliatiM 2003 The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry. Development 130 2303 2316

20. BisgroveBWEssnerJJYostHJ 2000 Multiple pathways in the midline regulate concordant brain, heart and gut left-right asymmetry. Development 127 3567 3579

21. BrandMHeisenbergCPWargaRMPelegriFKarlstromRO 1996 Mutations affecting development of the midline and general body shape during zebrafish embryogenesis. Development 123 129 142

22. ChenJNvan EedenFJWarrenKSChinANusslein-VolhardC 1997 Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish. Development 124 4373 4382

23. LiaoECZonLI 1999 Simple sequence-length polymorphism analysis. Methods Cell Biol 60 181 183

24. FanXHagosEGXuBSiasCKawakamiK 2007 Nodal signals mediate interactions between the extra-embryonic and embryonic tissues in zebrafish. Dev Biol 310 363 378

25. KikuchiYTrinhLAReiterJFAlexanderJYelonD 2000 The zebrafish bonnie and clyde gene encodes a Mix family homeodomain protein that regulates the generation of endodermal precursors. Genes Dev 14 1279 1289

26. RandallRAGermainSInmanGJBatesPAHillCS 2002 Different Smad2 partners bind a common hydrophobic pocket in Smad2 via a defined proline-rich motif. EMBO J 21 145 156

27. TrinhLAMeyerDStainierDY 2003 The Mix family homeodomain gene bonnie and clyde functions with other components of the Nodal signaling pathway to regulate neural patterning in zebrafish. Development 130 4989 4998

28. RyanKGarrettNMitchellAGurdonJB 1996 Eomesodermin, a key early gene in Xenopus mesoderm differentiation. Cell 87 989 1000

29. FukudaMTakahashiSHaramotoYOnumaYKimYJ 2010 Zygotic VegT is required for Xenopus paraxial mesoderm formation and is regulated by Nodal signaling and Eomesodermin. Int J Dev Biol 54 81 92

30. RussAPWattlerSColledgeWHAparicioSACarltonMB 2000 Eomesodermin is required for mouse trophoblast development and mesoderm formation. Nature 404 95 99

31. ArnoldSJHofmannUKBikoffEKRobertsonEJ 2008 Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse. Development 135 501 511

32. BruceAEHowleyCZhouYVickersSLSilverLM 2003 The maternally expressed zebrafish T-box gene eomesodermin regulates organizer formation. Development 130 5503 5517

33. BjornsonCRGriffinKJFarrGH3rdTerashimaAHimedaC 2005 Eomesodermin is a localized maternal determinant required for endoderm induction in zebrafish. Dev Cell 9 523 533

34. PicozziPWangFCronkKRyanK 2009 Eomesodermin requires transforming growth factor-beta/activin signaling and binds Smad2 to activate mesodermal genes. J Biol Chem 284 2397 2408

35. AlexanderJStainierDY 1999 A molecular pathway leading to endoderm formation in zebrafish. Curr Biol 9 1147 1157

36. NorrisDPBrennanJBikoffEKRobertsonEJ 2002 The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo. Development 129 3455 3468

37. OsadaSISaijohYFrischAYeoCYAdachiH 2000 Activin/nodal responsiveness and asymmetric expression of a Xenopus nodal-related gene converge on a FAST-regulated module in intron 1. Development 127 2503 2514

38. SaijohYAdachiHSakumaRYeoCYYashiroK 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

39. HalpernMEHoRKWalkerCKimmelCB 1993 Induction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation. Cell 75 99 111

40. GriffinKJAmacherSLKimmelCBKimelmanD 1998 Molecular identification of spadetail: regulation of zebrafish trunk and tail mesoderm formation by T-box genes. Development 125 3379 3388

41. IzziLSilvestriCvon BothILabbeEZakinL 2007 Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development. EMBO J 26 3132 3143

42. LabbeESilvestriCHoodlessPAWranaJLAttisanoL 1998 Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2. Mol Cell 2 109 120

43. GravesBJCowleyDOGoetzTLPetersenJMJonsenMD 1998 Autoinhibition as a transcriptional regulatory mechanism. Cold Spring Harb Symp Quant Biol 63 621 629

44. HagmanJGrosschedlR 1992 An inhibitory carboxyl-terminal domain in Ets-1 and Ets-2 mediates differential binding of ETS family factors to promoter sequences of the mb-1 gene. Proc Natl Acad Sci U S A 89 8889 8893

45. LimFKrautNFramptomJGrafT 1992 DNA binding by c-Ets-1, but not v-Ets, is repressed by an intramolecular mechanism. EMBO J 11 643 652

46. WasylykCKerckaertJPWasylykB 1992 A novel modulator domain of Ets transcription factors. Genes Dev 6 965 974

47. BaetzKAndrewsB 1999 Regulation of cell cycle transcription factor Swi4 through auto-inhibition of DNA binding. Mol Cell Biol 19 6729 6741

48. von BothISilvestriCErdemirTLickertHWallsJR 2004 Foxh1 is essential for development of the anterior heart field. Dev Cell 7 331 345

49. PeiWFeldmanB 2009 Identification of common and unique modifiers of zebrafish midline bifurcation and cyclopia. Dev Biol 326 201 211

50. ZhangYShaoMWangLLiuZGaoM 2010 Ethanol exposure affects cell movement during gastrulation and induces split axes in zebrafish embryos. Int J Dev Neurosci 28 283 288

51. CheaHKWrightCVSwallaBJ 2005 Nodal signaling and the evolution of deuterostome gastrulation. Dev Dyn 234 269 278

52. LaprazFRottingerEDubocVRangeRDuloquinL 2006 RTK and TGF-beta signaling pathways genes in the sea urchin genome. Dev Biol 300 132 152

53. GrandeCPatelNH 2009 Nodal signalling is involved in left-right asymmetry in snails. Nature 457 1007 1011

54. KispertAHerrmannBGLeptinMReuterR 1994 Homologs of the mouse Brachyury gene are involved in the specification of posterior terminal structures in Drosophila, Tribolium, and Locusta. Genes Dev 8 2137 2150

55. AdellTGrebenjukVAWiensMMullerWE 2003 Isolation and characterization of two T-box genes from sponges, the phylogenetically oldest metazoan taxon. Dev Genes Evol 213 421 434

56. LarrouxCLukeGNKoopmanPRokhsarDSShimeldSM 2008 Genesis and expansion of metazoan transcription factor gene classes. Mol Biol Evol 25 980 996

57. ZhuGMullerEGAmacherSLNorthropJLDavisTN 1993 A dosage-dependent suppressor of a temperature-sensitive calmodulin mutant encodes a protein related to the fork head family of DNA-binding proteins. Mol Cell Biol 13 1779 1787

58. MazetFYuJKLiberlesDAHollandLZShimeldSM 2003 Phylogenetic relationships of the Fox (Forkhead) gene family in the Bilateria. Gene 316 79 89

59. YuJKMazetFChenYTHuangSWJungKC 2008 The Fox genes of Branchiostoma floridae. Dev Genes Evol 218 629 638

60. TuQBrownCTDavidsonEHOliveriP 2006 Sea urchin Forkhead gene family: phylogeny and embryonic expression. Dev Biol 300 49 62

61. KuglerJEPassamaneckYJFeldmanTGBehJRegnierTW 2008 Evolutionary conservation of vertebrate notochord genes in the ascidian Ciona intestinalis. Genesis 46 697 710

62. StainierDY 2002 A glimpse into the molecular entrails of endoderm formation. Genes Dev 16 893 907

63. DrieverWSolnica-KrezelLSchierAFNeuhaussSCMalickiJ 1996 A genetic screen for mutations affecting embryogenesis in zebrafish. Development 123 37 46

64. HaffterPGranatoMBrandMMCHammerschmidtM 1996 The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 123 1 36

65. ThisseCThisseB 2008 High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc 3 59 69

66. Schulte-MerkerSHoRKHerrmannBGNusslein-VolhardC 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

67. StachelSEGrunwaldDJMyersPZ 1993 Lithium perturbation and goosecoid expression identify a dorsal specification pathway in the pregastrula zebrafish. Development 117 1261 1274

68. AlexanderJRothenbergMHenryGLStainierDY 1999 casanova plays an early and essential role in endoderm formation in zebrafish. Dev Biol 215 343 357

69. StrahleUBladerPHenriqueDInghamPW 1993 Axial, a zebrafish gene expressed along the developing body axis, shows altered expression in cyclops mutant embryos. Genes Dev 7 1436 1446

70. KikuchiYAgathonAAlexanderJThisseCWaldronS 2001 casanova encodes a novel Sox-related protein necessary and sufficient for early endoderm formation in zebrafish. Genes Dev 15 1493 1505

71. TalbotWSTrevarrowBHalpernMEMelbyAEFarrG 1995 A homeobox gene essential for zebrafish notochord development. Nature 378 150 157

72. KraussSJohansenTKorzhVFjoseA 1991 Expression of the zebrafish paired box gene pax[zf-b] during early neurogenesis. Development 113 1193 1206

73. HerbomelPThisseBThisseC 1999 Ontogeny and behaviour of early macrophages in the zebrafish embryo. Development 126 3735 3745

74. KraussSConcordetJPInghamPW 1993 A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75 1431 1444

75. BisgroveBWEssnerJJYostHJ 1999 Regulation of midline development by antagonism of lefty and nodal signaling. Development 126 3253 3262

76. ErterCESolnica-KrezelLWrightCV 1998 Zebrafish nodal-related 2 encodes an early mesendodermal inducer signaling from the extraembryonic yolk syncytial layer. Dev Biol 204 361 372

77. RebagliatiMRToyamaRHaffterPDawidIB 1998 cyclops encodes a nodal-related factor involved in midline signaling. Proc Natl Acad Sci U S A 95 9932 9937

78. YanYLHattaKRigglemanBPostlethwaitJH 1995 Expression of a type II collagen gene in the zebrafish embryonic axis. Dev Dyn 203 363 376

79. SokolSChristianJLMoonRTMeltonDA 1991 Injected Wnt RNA induces a complete body axis in Xenopus embryos. Cell 67 741 752

80. BakerJCHarlandRM 1996 A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. Genes Dev 10 1880 1889

81. FeldmanBStempleDL 2001 Morpholino phenocopies of sqt, oep, and ntl mutations. Genesis 30 175 177

82. KarlenSRebagliatiM 2001 A morpholino phenocopy of the cyclops mutation. Genesis 30 126 128

83. AokiTSchweinsbergSManassonJSchedlP 2008 A stage-specific factor confers Fab-7 boundary activity during early embryogenesis in Drosophila. Mol Cell Biol 28 1047 1060