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Cited by 78Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanisms

TBX3 Directs Cell-Fate Decision toward Mesendoderm

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Weidgang, Clair E., Russell, Ronan, Tata, Purushothama R., Kühl, Susanne J., Illing, Anett, Müller, Martin, Lin, Qiong, Brunner, Cornelia +15 more·2013·Stem Cell Reports
DOI 10.1016/j.stemcr.2013.08.002PMC PMC3849240
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Abstract

Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.

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  • TBX3 is critically involved in pluripotency maintenance and lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells.

    “Finally, TBX3 is not only critically involved in pluripotency maintenance but also in lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells [11–17].”

    From TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration (2023) · cites this paper as [13]

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References 43 · Cited by 78

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  1. Bamshad M. Lin R.C. Law D.J. Watkins W.C. Krakowiak P.A. Moore M.E. Franceschini P. Lala R. Holmes L.B. Gebuhr T.C. Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome Nat. Genet. 16 1997 311 315 9207801
  2. Blair K. Wray J. Smith A. The liberation of embryonic stem cells PLoS Genet. 7 2011 e1002019 21490948 PMC3072365
  3. Brennan J. Lu C.C. Norris D.P. Rodriguez T.A. Beddington R.S. Robertson E.J. Nodal signalling in the epiblast patterns the early mouse embryo Nature 411 2001 965 969 11418863
  4. Carreira S. Dexter T.J. Yavuzer U. Easty D.J. Goding C.R. Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter Mol. Cell. Biol. 18 1998 5099 5108 9710594 PMC109095
  5. Chapman D.L. Garvey N. Hancock S. Alexiou M. Agulnik S.I. Gibson-Brown J.J. Cebra-Thomas J. Bollag R.J. Silver L.M. Papaioannou V.E. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development Dev. Dyn. 206 1996 379 390 8853987
  6. Cheng X. Ying L. Lu L. Galvão A.M. Mills J.A. Lin H.C. Kotton D.N. Shen S.S. Nostro M.C. Choi J.K. Self-renewing endodermal progenitor lines generated from human pluripotent stem cells Cell Stem Cell 10 2012 371 384 22482503 PMC3580854
  7. Cho G.S. Choi S.C. Park E.C. Han J.K. Role of Tbx2 in defining the territory of the pronephric nephron Development 138 2011 465 474 21205791
  8. Christodoulou C. Longmire T.A. Shen S.S. Bourdon A. Sommer C.A. Gadue P. Spira A. Gouon-Evans V. Murphy G.J. Mostoslavsky G. Kotton D.N. Mouse ES and iPS cells can form similar definitive endoderm despite differences in imprinted genes J. Clin. Invest. 121 2011 2313 2325 21537085 PMC3104741
  9. Davenport T.G. Jerome-Majewska L.A. Papaioannou V.E. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome Development 130 2003 2263 2273 12668638
  10. Finger J.H. Smith C.M. Hayamizu T.F. McCright I.J. Eppig J.T. Kadin J.A. Richardson J.E. Ringwald M. The mouse Gene Expression Database (GXD): 2011 update Nucleic Acids Res. 39 Database issue 2011 D835 D841 21062809 PMC3013713
  11. Frank D.U. Carter K.L. Thomas K.R. Burr R.M. Bakker M.L. Coetzee W.A. Tristani-Firouzi M. Bamshad M.J. Christoffels V.M. Moon A.M. Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis Proc. Natl. Acad. Sci. USA 109 2012 E154 E163 22203979 PMC3271904
  12. Gessert S. Kühl M. Comparative gene expression analysis and fate mapping studies suggest an early segregation of cardiogenic lineages in Xenopus laevis Dev. Biol. 334 2009 395 408 19660447
  13. Goering L.M. Hoshijima K. Hug B. Bisgrove B. Kispert A. Grunwald D.J. An interacting network of T-box genes directs gene expression and fate in the zebrafish mesoderm Proc. Natl. Acad. Sci. USA 100 2003 9410 9415 12883008 PMC170932
  14. Guo G. Huss M. Tong G.Q. Wang C. Li Sun L. Clarke N.D. Robson P. Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst Dev. Cell 18 2010 675 685 20412781
  15. Guzman-Ayala M. Lee K.L. Mavrakis K.J. Goggolidou P. Norris D.P. Episkopou V. Graded Smad2/3 activation is converted directly into levels of target gene expression in embryonic stem cells PLoS ONE 4 2009 e4268 19172185 PMC2627943
  16. Hadjantonakis A.K. Pisano E. Papaioannou V.E. Tbx6 regulates left/right patterning in mouse embryos through effects on nodal cilia and perinodal signaling PLoS ONE 3 2008 e2511 18575602 PMC2427182
  17. Han J. Yuan P. Yang H. Zhang J. Soh B.S. Li P. Lim S.L. Cao S. Tay J. Orlov Y.L. Tbx3 improves the germ-line competency of induced pluripotent stem cells Nature 463 2010 1096 1100 20139965 PMC2901797
  18. Hoogaars W.M. Engel A. Brons J.F. Verkerk A.O. de Lange F.J. Wong L.Y. Bakker M.L. Clout D.E. Wakker V. Barnett P. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria Genes Dev. 21 2007 1098 1112 17473172 PMC1855235
  19. Horsthuis T. Buermans H.P. Brons J.F. Verkerk A.O. Bakker M.L. Wakker V. Clout D.E. Moorman A.F. ’t Hoen P.A. Christoffels V.M. Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic reporter Circ. Res. 105 2009 61 69 19498200
  20. Iacovino M. Bosnakovski D. Fey H. Rux D. Bajwa G. Mahen E. Mitanoska A. Xu Z. Kyba M. Inducible cassette exchange: a rapid and efficient system enabling conditional gene expression in embryonic stem and primary cells Stem Cells 29 2011 1580 1588 22039605 PMC3622722
  21. Kartikasari A.E. Zhou J.X. Kanji M.S. Chan D.N. Sinha A. Grapin-Botton A. Magnuson M.A. Lowry W.E. Bhushan A. The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation EMBO J. 32 2013 1393 1408 23584530 PMC3655467
  22. Kleger A. Busch T. Liebau S. Prelle K. Paschke S. Beil M. Rolletschek A. Wobus A. Wolf E. Adler G. Seufferlein T. The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse embryonic stem cells and human promyelocytic leukaemia cells Cell. Signal. 19 2007 367 377 16978842
  23. Kleger A. Seufferlein T. Malan D. Tischendorf M. Storch A. Wolheim A. Latz S. Protze S. Porzner M. Proepper C. Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells Circulation 122 2010 1823 1836 20956206
  24. Liebau S. Vaida B. Proepper C. Grissmer S. Storch A. Boeckers T.M. Dietl P. Wittekindt O.H. Formation of cellular projections in neural progenitor cells depends on SK3 channel activity J. Neurochem. 101 2007 1338 1350 17459146
  25. Mesbah K. Rana M.S. Francou A. van Duijvenboden K. Papaioannou V.E. Moorman A.F. Kelly R.G. Christoffels V.M. Identification of a Tbx1/Tbx2/Tbx3 genetic pathway governing pharyngeal and arterial pole morphogenesis Hum. Mol. Genet. 21 2012 1217 1229 22116936 PMC3491916
  26. Morris S.A. Grewal S. Barrios F. Patankar S.N. Strauss B. Buttery L. Alexander M. Shakesheff K.M. Zernicka-Goetz M. Dynamics of anterior-posterior axis formation in the developing mouse embryo Nat Commun 3 2012 673 22334076 PMC3293425
  27. Pereira L.A. Wong M.S. Lim S.M. Sides A. Stanley E.G. Elefanty A.G. Brachyury and related Tbx proteins interact with the Mixl1 homeodomain protein and negatively regulate Mixl1 transcriptional activity PLoS ONE 6 2011 e28394 22164283 PMC3229578
  28. Price F.D. Yin H. Jones A. van Ijcken W. Grosveld F. Rudnicki M.A. Canonical Wnt signaling induces a primitive endoderm metastable state in mouse embryonic stem cells Stem Cells 31 2012 752 764 23307624
  29. Singh R. Hoogaars W.M. Barnett P. Grieskamp T. Rana M.S. Buermans H. Farin H.F. Petry M. Heallen T. Martin J.F. Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation Cell. Mol. Life Sci. 69 2012 1377 1389 22130515 PMC3314179
  30. Smyth G.K. Linear models and empirical bayes methods for assessing differential expression in microarray experiments Stat. Appl. Genet. Mol. Biol. 3 2004 Article3 16646809
  31. Solloway M.J. Robertson E.J. Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup Development 126 1999 1753 1768 10079236
  32. Song J. Oh S.P. Schrewe H. Nomura M. Lei H. Okano M. Gridley T. Li E. The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice Dev. Biol. 213 1999 157 169 10452853
  33. Stefanovic S. Abboud N. Désilets S. Nury D. Cowan C. Pucéat M. Interplay of Oct4 with Sox2 and Sox17: a molecular switch from stem cell pluripotency to specifying a cardiac fate J. Cell Biol. 186 2009 665 673 19736317 PMC2742180
  34. Tada S. Era T. Furusawa C. Sakurai H. Nishikawa S. Kinoshita M. Nakao K. Chiba T. Nishikawa S. Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture Development 132 2005 4363 4374 16141227
  35. Takabatake Y. Takabatake T. Sasagawa S. Takeshima K. Conserved expression control and shared activity between cognate T-box genes Tbx2 and Tbx3 in connection with Sonic hedgehog signaling during Xenopus eye development Dev. Growth Differ. 44 2002 257 271 12175361
  36. Tazumi S. Yabe S. Yokoyama J. Aihara Y. Uchiyama H. PMesogenin1 and 2 function directly downstream of Xtbx6 in Xenopus somitogenesis and myogenesis Dev. Dyn. 237 2008 3749 3761 19035338
  37. Thomson M. Liu S.J. Zou L.N. Smith Z. Meissner A. Ramanathan S. Pluripotency factors in embryonic stem cells regulate differentiation into germ layers Cell 145 2011 875 889 21663792 PMC5603300

Authors
Weidgang, C. E., Russell, R., Tata, P. R., Kühl, S. J., Illing, A., Müller, M., Lin, Q., Brunner, C., Boeckers, T. M., Bauer, K., Kartikasari, A. E. R., Guo, Y., Radenz, M., Bernemann, C., Weiß, M., Seufferlein, T., Zenke, M., Iacovino, M., Kyba, M., Schöler, H. R., Kühl, M., Liebau, S., & Kleger, A.
Affiliations
  • Universität Ulm (DE)
  • RWTH Aachen University (DE)
  • University of California, Los Angeles (US)
  • Max Planck Institute for Molecular Biomedicine (DE)
  • University Medical Center Freiburg (DE)
  • University of Minnesota (US)
Corresponding author
  • Liebau, Stefan
  • Kleger, Alexander
ORCID
Venue
Stem Cell Reports
Publisher
Elsevier BV
Published
2013-09
Volume
1
Issue
3
Pages
248-265
ISSN
2213-6711 (ISSN-L)
DOI
10.1016/j.stemcr.2013.08.002
PMC
PMC3849240
OpenAlex
W2075809760
Cited by
78
References
43
Citations by year
2026: 4 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 10 · 2018: 7 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 6 · 2013: 1
FWCI
4.18
Type
journal article
Language
en
Update notices
erratum (2014-05-06)
Open access
Licence
Locations
  • Stem Cell Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
  • RWTH Publications (RWTH Aachen) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
TBX3, mesendoderm specification, cell fate determination, embryonic stem cells, TBX2, gastrulation, transcriptional regulation, pluripotency, lineage commitment, Xenopus embryo, mouse embryo
MeSH terms
Animals, Cell Differentiation, Mesoderm, Xenopus, Gene Expression Regulation, Developmental, Cell Lineage, T-Box Domain Proteins, Mice, Smad2 Protein, Embryonic Stem Cells, Gastrulation, Nodal Protein

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