Genomes and Genes
Gene Symbol: Tbx6
Description: T-box 6
Alias: T-box transcription factor TBX6, T-box protein 6, rib-vertebrae
- Chapman D, Agulnik I, Hancock S, Silver L, Papaioannou V. Tbx6, a mouse T-Box gene implicated in paraxial mesoderm formation at gastrulation. Dev Biol. 1996;180:534-42 pubmed..We have previously reported the discovery of six new mouse T-box genes, Tbx1-Tbx6, and described the expression patterns of Tbx1-Tbx5 (Bollag et al., 1994; Agulnik et al., 1996; Chapman et al...
- Chapman D, Papaioannou V. Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6. Nature. 1998;391:695-7 pubmed..We have previously described a mouse T-box gene, Tbx6, which codes for a putative DNA-binding protein...
- Yasuhiko Y, Haraguchi S, Kitajima S, Takahashi Y, Kanno J, Saga Y. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression. Proc Natl Acad Sci U S A. 2006;103:3651-6 pubmed..In our current study, we show that a T-box transcription factor, Tbx6, is essential for Mesp2 expression...
- Wittler L, Shin E, Grote P, Kispert A, Beckers A, Gossler A, et al. Expression of Msgn1 in the presomitic mesoderm is controlled by synergism of WNT signalling and Tbx6. EMBO Rep. 2007;8:784-9 pubmed..These findings emphasize the crucial role of WNT signalling in the control of psm formation, maturation and segmentation. ..
- Niwa Y, Masamizu Y, Liu T, Nakayama R, Deng C, Kageyama R. The initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and notch signaling in the somite segmentation clock. Dev Cell. 2007;13:298-304 pubmed..We thus propose that Hes7 oscillation is initiated by Fgf signaling and propagated/maintained anteriorly by Notch signaling. ..
- Sun X, Meyers E, Lewandoski M, Martin G. Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo. Genes Dev. 1999;13:1834-46 pubmed..This study identifies Fgf8 as a gene essential for gastrulation and shows that signaling via FGF8 and/or FGF4 is required for cell migration away from the primitive streak. ..
- White P, Chapman D. Dll1 is a downstream target of Tbx6 in the paraxial mesoderm. Genesis. 2005;42:193-202 pubmedb>Tbx6 is a member of the T-box family of transcription factors...
- Yamaguchi T, Takada S, Yoshikawa Y, Wu N, McMahon A. T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification. Genes Dev. 1999;13:3185-90 pubmed..Embryos lacking the T-box-containing transcription factors, Brachyury or Tbx6, also lack paraxial mesoderm...
- Takemoto T, Uchikawa M, Yoshida M, Bell D, Lovell Badge R, Papaioannou V, et al. Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells. Nature. 2011;470:394-8 pubmed publisher..b>Tbx6 null mutant mouse embryos which produce ectopic neural tubes at the expense of paraxial mesoderm must provide a ..
- Hofmann M, Schuster Gossler K, Watabe Rudolph M, Aulehla A, Herrmann B, Gossler A. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos. Genes Dev. 2004;18:2712-7 pubmed..LEF/TCF factors cooperate with TBX6 to activate transcription from the Dll1 promoter in vitro...
- Aulehla A, Wiegraebe W, Baubet V, Wahl M, Deng C, Taketo M, et al. A beta-catenin gradient links the clock and wavefront systems in mouse embryo segmentation. Nat Cell Biol. 2008;10:186-93 pubmed..This gradient of nuclear beta-catenin defines the size of the oscillatory field and controls key aspects of PSM maturation and segment formation, emphasizing the central role of Wnt signalling in this process. ..
- Ciruna B, Rossant J. FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. Dev Cell. 2001;1:37-49 pubmed..we show that FGFR1 functions in mesoderm cell fate specification by positively regulating Brachyury and Tbx6 expression...
- Arnold S, Hofmann U, Bikoff E, Robertson E. Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse. Development. 2008;135:501-11 pubmed publisher..Collectively, our experiments establish that Eomes is a key regulator of anteroposterior axis formation, EMT and definitive endoderm specification in the mouse. ..
- White P, Farkas D, McFadden E, Chapman D. Defective somite patterning in mouse embryos with reduced levels of Tbx6. Development. 2003;130:1681-90 pubmed..The T-box transcription factor, Tbx6, is expressed in the paraxial mesoderm but is downregulated as somites develop...
- Farin H, Bussen M, Schmidt M, Singh M, Schuster Gossler K, Kispert A. Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors. J Biol Chem. 2007;282:25748-59 pubmed..and Nkx2-5 and competes Tbx5-mediated activation of the cardiac Natriuretic peptide precursor type a-promoter and that ectopic expression of Tbx18 down-regulates Tbx6-activated Delta-like 1 expression in the somitic mesoderm in vivo.
- Chapman D, Cooper Morgan A, Harrelson Z, Papaioannou V. Critical role for Tbx6 in mesoderm specification in the mouse embryo. Mech Dev. 2003;120:837-47 pubmedb>Tbx6 is a member of the T-box family of transcription factor genes. Two mutant alleles of this gene establish that Tbx6 is involved in both the specification and patterning of the somites along the entire length of the embryo...
- Yasuhiko Y, Kitajima S, Takahashi Y, Oginuma M, Kagiwada H, Kanno J, et al. Functional importance of evolutionally conserved Tbx6 binding sites in the presomitic mesoderm-specific enhancer of Mesp2. Development. 2008;135:3511-9 pubmed publisherThe T-box transcription factor Tbx6 controls the expression of Mesp2, which encodes a basic helix-loop-helix transcription factor that has crucial roles in somitogenesis...
- Oginuma M, Takahashi Y, Kitajima S, Kiso M, Kanno J, Kimura A, et al. The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite. Development. 2010;137:1515-22 pubmed publisher..This indicates that the initial somite pattern can be defined as a direct output of the segmentation clock...
- Nowotschin S, Ferrer Vaquer A, CONCEPCION D, Papaioannou V, Hadjantonakis A. Interaction of Wnt3a, Msgn1 and Tbx6 in neural versus paraxial mesoderm lineage commitment and paraxial mesoderm differentiation in the mouse embryo. Dev Biol. 2012;367:1-14 pubmed publisher..This network hinges on three key factors, Wnt3a, Msgn1 and Tbx6, each of which is critical for paraxial mesoderm formation, since absence of any one of these factors results in ..
- Watabe Rudolph M, Schlautmann N, Papaioannou V, Gossler A. The mouse rib-vertebrae mutation is a hypomorphic Tbx6 allele. Mech Dev. 2002;119:251-6 pubmed..By fine genetic mapping and complementation testing we have identified Tbx6, a gene essential for paraxial mesoderm formation, as the gene mutated in rv...
- Toyo oka K, Mori D, Yano Y, Shiota M, Iwao H, Goto H, et al. Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation. J Cell Biol. 2008;180:1133-47 pubmed publisher..Our work uncovers a unique regulatory mechanism of MT organization by PP4c through its targets Cdk1 and NDEL1 via regulation of katanin p60 distribution. ..
- Dunty W, Biris K, Chalamalasetty R, Taketo M, Lewandoski M, Yamaguchi T. Wnt3a/beta-catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation. Development. 2008;135:85-94 pubmed..Ripply2 in the PSM through the activation of the Notch ligand Dll1 and the mesodermal transcription factors T and Tbx6. Spatial restriction of Ripply2 to the anterior PSM is ensured by the Wnt3a/beta-catenin-mediated repression of ..
- Qian L, Mahaffey J, Alcorn H, Anderson K. Tissue-specific roles of Axin2 in the inhibition and activation of Wnt signaling in the mouse embryo. Proc Natl Acad Sci U S A. 2011;108:8692-7 pubmed publisher..The results indicate that although increased stability of Axin2 leads to a loss of canonical Wnt signaling in most tissues, stabilized Axin2 enhances Wnt pathway activity in a specific progenitor population in the late primitive streak. ..
- Gonzalez A, Manosalva I, Liu T, Kageyama R. Control of Hes7 expression by Tbx6, the Wnt pathway and the chemical Gsk3 inhibitor LiCl in the mouse segmentation clock. PLoS ONE. 2013;8:e53323 pubmed publisher..in transgenic mouse embryos and have identified an essential 400 bp region, which contains binding sites of Tbx6 and the Wnt signaling effector Lef1...
- Chalamalasetty R, Garriock R, Dunty W, Kennedy M, Jailwala P, Si H, et al. Mesogenin 1 is a master regulator of paraxial presomitic mesoderm differentiation. Development. 2014;141:4285-97 pubmed publisher..Our data provide new insights into how cell fate decisions are imposed by the expression of a single transcriptional regulator. ..
- Dear T, Hainzl T, Follo M, Nehls M, Wilmore H, Matena K, et al. Identification of interaction partners for the basic-helix-loop-helix protein E47. Oncogene. 1997;14:891-8 pubmed..A cDNA encoding part of the nucleolin protein sequence interacted with the E47 basic-helix-loop-helix only when fused to a beta-galactosidase tag. ..
- Perea Gomez A, Shawlot W, Sasaki H, Behringer R, Ang S. HNF3beta and Lim1 interact in the visceral endoderm to regulate primitive streak formation and anterior-posterior polarity in the mouse embryo. Development. 1999;126:4499-511 pubmed..Moreover, HNF3beta (-)(/)(-);Lim1(-)(/)(-) mutant embryos also exhibit defects in mesoderm patterning that are likely due to lack of specification of anterior primitive streak cells. ..
- Nacke S, Schafer R, Habré de Angelis M, Mundlos S. Mouse mutant "rib-vertebrae" (rv): a defect in somite polarity. Dev Dyn. 2000;219:192-200 pubmed..We have mapped rv to a region on chromosome 7 that is syntenic to human chromosomes 11p, 10q, and 11p. rv is phenotypically similar to human vertebral malformations syndromes and can serve as a model for these conditions. ..
- van Rooijen C, Simmini S, Bialecka M, Neijts R, van de Ven C, Beck F, et al. Evolutionarily conserved requirement of Cdx for post-occipital tissue emergence. Development. 2012;139:2576-83 pubmed publisher..Cdx requirement for the post-head section of the axis is ancestral as it takes place in arthropods as well. ..
- Girós A, Grgur K, Gossler A, Costell M. α5β1 integrin-mediated adhesion to fibronectin is required for axis elongation and somitogenesis in mice. PLoS ONE. 2011;6:e22002 pubmed publisher..Thus, α5β1-mediated adhesion to FN in the PSM regulates the dynamics of membrane protrusions and cell-to-cell communication essential for elongation and segmentation of the body axis. ..
- Perea Gomez A, Vella F, Shawlot W, Oulad Abdelghani M, Chazaud C, Meno C, et al. Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Dev Cell. 2002;3:745-56 pubmed..Both antagonists are also required for proper patterning of the primitive streak. ..
- Gavrilov S, Nührenberg T, Ashton A, Peng C, Moore J, Konstantinidis K, et al. Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells. Differentiation. 2012;84:176-84 pubmed publisher..Expression of the transcription factor Tbx6 was found to increase during cardiac myocyte differentiation and to decrease during neural differentiation...
- Oginuma M, Niwa Y, Chapman D, Saga Y. Mesp2 and Tbx6 cooperatively create periodic patterns coupled with the clock machinery during mouse somitogenesis. Development. 2008;135:2555-62 pubmed publisher..We also find that Mesp2 transcription is spatially defined by Tbx6: Mesp2 transcription and Tbx6 protein initially share an identical anterior border in the PSM, but once translated, ..
- Galceran J, Farinas I, Depew M, Clevers H, Grosschedl R. Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice. Genes Dev. 1999;13:709-17 pubmed..Together, these data provide evidence for a redundant role of LEF-1 and TCF-1 in Wnt signaling during mouse development. ..
- Sasaki N, Kiso M, Kitagawa M, Saga Y. The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis. Development. 2011;138:55-64 pubmed publisher..Surprisingly, this function of Mesp2 is found to be independent of its function as a transcription factor. Together, these data demonstrate that Mesp2 is a novel component involved in the suppression of Notch target genes...
- Shier P, Hofstra C, Ma X, Wu Y, Ngo K, Fung Leung W. Tbt-1, a new T-box transcription factor induced in activated Th1 and CD8+ T cells. Immunogenetics. 2000;51:771-8 pubmed..In addition, phylogenetic analyses indicate that Tbt-1 co-evolved with adaptive immune responses. Thus, Tbt-1 is the first T-box transcription factor shown to be specific for Th1 cell differentiation. ..
- Wehn A, Chapman D. Tbx18 and Tbx15 null-like phenotypes in mouse embryos expressing Tbx6 in somitic and lateral plate mesoderm. Dev Biol. 2010;347:404-13 pubmed publisher..In the mouse, Tbx6 is expressed in the primitive streak and presomitic mesoderm, and is sharply down-regulated upon segmentation of ..
- Chen Y, Liu B, Zhou Z, Hu R, Fei C, Xie Z, et al. Smad6 inhibits the transcriptional activity of Tbx6 by mediating its degradation. J Biol Chem. 2009;284:23481-90 pubmed publisher..Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal...
- Pereira L, Wong M, Lim S, Sides A, Stanley E, Elefanty A. Brachyury and related Tbx proteins interact with the Mixl1 homeodomain protein and negatively regulate Mixl1 transcriptional activity. PLoS ONE. 2011;6:e28394 pubmed publisher..Our results indicate that the activity of Mixl1 can be modulated by protein-protein interactions and that T-box factors can function as negative regulators of Mixl1 activity. ..
- Chalamalasetty R, Dunty W, Biris K, Ajima R, Iacovino M, Beisaw A, et al. The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program. Nat Commun. 2011;2:390 pubmed publisher..Msgn1 also indirectly regulates cyclic genes in the Fgf and Wnt pathways. Thus, Msgn1 is a central component of a transcriptional cascade that translates a spatial Wnt3a gradient into a temporal pattern of clock gene expression. ..
- Beckers J, Schlautmann N, Gossler A. The mouse rib-vertebrae mutation disrupts anterior-posterior somite patterning and genetically interacts with a Delta1 null allele. Mech Dev. 2000;95:35-46 pubmed..However, fine genetic mapping places rv into an interval on chromosome seven that does not contain a gene encoding a known component of the Notch signaling pathway. ..
- Chen M, Maloney J, Kallop D, Atwal J, Tam S, Baer K, et al. Spatially coordinated kinase signaling regulates local axon degeneration. J Neurosci. 2012;32:13439-53 pubmed..Additionally, we identify the dleu2/mir15a/16-1 cluster, previously characterized as a regulator of B-cell proliferation, and the transcription factor tbx6, as likely downstream effectors of GSK3β in axon degeneration.
- Jin J, Ding J. Cripto is required for mesoderm and endoderm cell allocation during mouse gastrulation. Dev Biol. 2013;381:170-8 pubmed publisher..These results demonstrate a critical role for Cripto during mouse gastrulation, especially in mesoderm and endoderm formation and allocation. ..
- Brown M, Yui K, Smith J, LeBoeuf R, Weng W, Umeda P, et al. The murine macrophage apoB-48 receptor gene (Apob-48r): homology to the human receptor. J Lipid Res. 2002;43:1181-91 pubmed....
- Salbaum J, Kruger C, MacGowan J, Herion N, Burk D, Kappen C. Novel Mode of Defective Neural Tube Closure in the Non-Obese Diabetic (NOD) Mouse Strain. Sci Rep. 2015;5:16917 pubmed publisher..We conclude that perturbed gastrulation not only explains the neurulation defects, but also provides a unifying etiology for the broad spectrum of congenital malformations in diabetic pregnancies. ..
- Satoh W, Gotoh T, Tsunematsu Y, Aizawa S, Shimono A. Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis. Development. 2006;133:989-99 pubmed..This study suggests that Wnt regulation by Sfrp1 and Sfrp2 is required for embryonic patterning. ..
- Guo Q, Li J. Distinct functions of the major Fgf8 spliceform, Fgf8b, before and during mouse gastrulation. Development. 2007;134:2251-60 pubmed....
- Bazzi H, Soroka E, Alcorn H, Anderson K. STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo. Proc Natl Acad Sci U S A. 2017;114:E10928-E10936 pubmed publisher..The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo. ..
- Javali A, Misra A, Leonavicius K, Acharyya D, Vyas B, Sambasivan R. Co-expression of Tbx6 and Sox2 identifies a novel transient neuromesoderm progenitor cell state. Development. 2017;144:4522-4529 pubmed publisher..The current model for the mechanism controlling NMP deployment invokes Tbx6, a T-box factor, to drive mesoderm differentiation of NMPs...
- Zhao X, Duester G. Effect of retinoic acid signaling on Wnt/beta-catenin and FGF signaling during body axis extension. Gene Expr Patterns. 2009;9:430-5 pubmed publisher..by Sprouty2 and Pea3 expression, and an expansion of Wnt/beta-catenin signaling detected by expression of Axin2, Tbx6, Cdx2, and Cdx4...
- Lewis S, Khoo P, De Young R, Steiner K, Wilcock C, Mukhopadhyay M, et al. Dkk1 and Wnt3 interact to control head morphogenesis in the mouse. Development. 2008;135:1791-801 pubmed publisher..These findings highlight that head development is sensitive to the level of WNT3 signalling and that DKK1 is the key antagonist that modulates WNT3 activity during anterior morphogenesis...
- Kelly O, Pinson K, Skarnes W. The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice. Development. 2004;131:2803-15 pubmed..The effect of reducing, but not eliminating, Wnt signaling in Lrp5(+/-);Lrp6(-/-) mutant embryos provides important insight into the interplay between Wnt, Fgf and Nodal signals in patterning the early mouse embryo. ..
- Zohn I, Li Y, Skolnik E, Anderson K, Han J, Niswander L. p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Cell. 2006;125:957-69 pubmed..Finally, p38 regulates E-cadherin protein expression downstream from NCK-interacting kinase (NIK) and independently of the regulation of transcription by Fibroblast Growth Factor (Fgf) signaling and Snail. ..
- Smith J. T-box genes: what they do and how they do it. Trends Genet. 1999;15:154-8 pubmed..An understanding of how the T-box genes act requires analysis of how their expression is controlled, identification of their target genes, and an insight into how different family members exert different effects. ..
- Sparrow D, Chapman G, Smith A, Mattar M, Major J, O Reilly V, et al. A mechanism for gene-environment interaction in the etiology of congenital scoliosis. Cell. 2012;149:295-306 pubmed publisher..Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction...
- Lopez T, Fan C. Dynamic CREB family activity drives segmentation and posterior polarity specification in mammalian somitogenesis. Proc Natl Acad Sci U S A. 2013;110:E2019-27 pubmed publisher..Together, these data support that the CREB family acts at the determination front to modulate Wnt signaling and strengthen Notch signaling as a means to orchestrate cells for somite segmentation and anterior/posterior patterning. ..
- Lange L, Marks M, Liu J, Wittler L, Bauer H, Piehl S, et al. Patterning and gastrulation defects caused by the tw18 lethal are due to loss of Ppp2r1a. Biol Open. 2017;6:752-764 pubmed publisher..Our work highlights the importance of phosphatase 2A in embryonic patterning, primitive streak formation, gastrulation, and mesoderm formation downstream of WNT and Nodal signaling. ..
- Naiche L, Holder N, Lewandoski M. FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis. Proc Natl Acad Sci U S A. 2011;108:4018-23 pubmed publisher..Furthermore, these data show that FGF action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM progenitor tissue. ..
- Savory J, Bouchard N, Pierre V, Rijli F, De Repentigny Y, Kothary R, et al. Cdx2 regulation of posterior development through non-Hox targets. Development. 2009;136:4099-110 pubmed publisher..We propose a model wherein Cdx2 functions as an integrator of caudalizing information by coordinating axial elongation and somite patterning through Hox-independent and -dependent pathways, respectively. ..
- Xie Y, Jüschke C, Esk C, Hirotsune S, Knoblich J. The phosphatase PP4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex. Neuron. 2013;79:254-65 pubmed publisher..Our results identify a key regulator of cortical development and demonstrate that changes in the orientation of progenitor division are responsible for the transition between symmetric and asymmetric cell division. ..
- Yamaguchi T, Bradley A, McMahon A, Jones S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development. 1999;126:1211-23 pubmed..The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells. ..
- Gregorieff A, Grosschedl R, Clevers H. Hindgut defects and transformation of the gastro-intestinal tract in Tcf4(-/-)/Tcf1(-/-) embryos. EMBO J. 2004;23:1825-33 pubmed..Our results reveal a novel role for Wnt signalling in early gut morphogenesis and suggest that specific Wnt-driven patterning events are determined by the unique tissue distribution of Tcf/Lef family members. ..