XB-ART-47737
Stem Cell Reports
January 1, 2013;
1
(3):
248-65.
TBX3 Directs Cell-Fate Decision toward Mesendoderm.
Weidgang CE
,
Russell R
,
Tata PR
,
Kühl SJ
,
Illing A
,
Müller M
,
Lin Q
,
Brunner C
,
Boeckers TM
,
Bauer K
,
Kartikasari AE
,
Guo Y
,
Radenz M
,
Bernemann C
,
Weiß M
,
Seufferlein T
,
Zenke M
,
Iacovino M
,
Kyba M
,
Schöler HR
,
Kühl M
,
Liebau S
,
Kleger A
.
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.
PubMed ID: 24319661
PMC ID: PMC3849240
Article link: Stem Cell Reports
Species referenced: Xenopus laevis
Genes referenced: alb bmp4 cer1 dpp4 eomes fgf2 foxa2 hhex isl1 klf5 klf9 lefty mespb myh6 myl7 nodal nodal1 pecam1 pou5f3.1 smad2 sox17a tbx2 tbx3 tbxt vegfa wnt3a
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References [+] :
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Bamshad, Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. 1997, Pubmed
Blair, The liberation of embryonic stem cells. 2011, Pubmed
Brennan, Nodal signalling in the epiblast patterns the early mouse embryo. 2001, Pubmed
Carreira, Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter. 1998, Pubmed
Chapman, Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. 1997, Pubmed
Cheng, Self-renewing endodermal progenitor lines generated from human pluripotent stem cells. 2012, Pubmed
Cho, Role of Tbx2 in defining the territory of the pronephric nephron. 2011, Pubmed , Xenbase
Christodoulou, Mouse ES and iPS cells can form similar definitive endoderm despite differences in imprinted genes. 2011, Pubmed
Davenport, Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. 2003, Pubmed
Finger, The mouse Gene Expression Database (GXD): 2011 update. 2010, Pubmed
Frank, Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis. 2012, Pubmed
Gessert, Comparative gene expression analysis and fate mapping studies suggest an early segregation of cardiogenic lineages in Xenopus laevis. 2009, Pubmed , Xenbase
Goering, An interacting network of T-box genes directs gene expression and fate in the zebrafish mesoderm. 2003, Pubmed
Guo, Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. 2010, Pubmed
Guzman-Ayala, Graded Smad2/3 activation is converted directly into levels of target gene expression in embryonic stem cells. 2009, Pubmed
Hadjantonakis, Tbx6 regulates left/right patterning in mouse embryos through effects on nodal cilia and perinodal signaling. 2008, Pubmed
Han, Tbx3 improves the germ-line competency of induced pluripotent stem cells. 2010, Pubmed
Hoogaars, Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. 2007, Pubmed
Horsthuis, Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic reporter. 2009, Pubmed
Iacovino, Inducible cassette exchange: a rapid and efficient system enabling conditional gene expression in embryonic stem and primary cells. 2011, Pubmed
Kartikasari, The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation. 2013, Pubmed
Kleger, Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells. 2010, Pubmed
Kleger, The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse embryonic stem cells and human promyelocytic leukaemia cells. 2007, Pubmed
Kwon, The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. 2008, Pubmed
Liebau, Formation of cellular projections in neural progenitor cells depends on SK3 channel activity. 2007, Pubmed
Lu, Dual functions of T-box 3 (Tbx3) in the control of self-renewal and extraembryonic endoderm differentiation in mouse embryonic stem cells. 2011, Pubmed
Mesbah, Identification of a Tbx1/Tbx2/Tbx3 genetic pathway governing pharyngeal and arterial pole morphogenesis. 2012, Pubmed
Morris, Dynamics of anterior-posterior axis formation in the developing mouse embryo. 2012, Pubmed
Niwa, A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. 2009, Pubmed
Pereira, Brachyury and related Tbx proteins interact with the Mixl1 homeodomain protein and negatively regulate Mixl1 transcriptional activity. 2011, Pubmed
Price, Canonical Wnt signaling induces a primitive endoderm metastable state in mouse embryonic stem cells. 2013, Pubmed
Singh, Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation. 2012, Pubmed
Smyth, Linear models and empirical bayes methods for assessing differential expression in microarray experiments. 2006, Pubmed
Solloway, Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup. 1999, Pubmed
Song, The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice. 1999, Pubmed , Xenbase
Stefanovic, Interplay of Oct4 with Sox2 and Sox17: a molecular switch from stem cell pluripotency to specifying a cardiac fate. 2009, Pubmed
Tada, Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture. 2005, Pubmed
Takabatake, Conserved expression control and shared activity between cognate T-box genes Tbx2 and Tbx3 in connection with Sonic hedgehog signaling during Xenopus eye development. 2002, Pubmed , Xenbase
Tazumi, PMesogenin1 and 2 function directly downstream of Xtbx6 in Xenopus somitogenesis and myogenesis. 2008, Pubmed , Xenbase
Thomson, Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. 2011, Pubmed
Weidgang, TBX3 Directs Cell-Fate Decision toward Mesendoderm. 2017, Pubmed
Ying, The ground state of embryonic stem cell self-renewal. 2008, Pubmed
Zorn, Vertebrate endoderm development and organ formation. 2009, Pubmed , Xenbase