Genomes and Genes
Gene Symbol: Tbx4
Description: T-box 4
Alias: 3930401C23, T-box transcription factor TBX4, T-box protein 4
- Davenport T, Jerome Majewska L, Papaioannou V. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Development. 2003;130:2263-73 pubmed
- Cebra Thomas J, Bromer J, Gardner R, Lam G, Sheipe H, Gilbert S. T-box gene products are required for mesenchymal induction of epithelial branching in the embryonic mouse lung. Dev Dyn. 2003;226:82-90 pubmed..oligonucleotides (AS ODNs) and in vitro culture of embryonic lungs, we demonstrate that the transcription factors Tbx4 and Tbx5 are critical for the expression of mesenchymal FGF10...
- Agarwal P, Wylie J, Galceran J, Arkhitko O, Li C, Deng C, et al. Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo. Development. 2003;130:623-33 pubmed..These data suggest common pathways for the differentiation and growth of embryonic structures downstream of T-box genes. ..
- Arora R, Metzger R, Papaioannou V. Multiple roles and interactions of Tbx4 and Tbx5 in development of the respiratory system. PLoS Genet. 2012;8:e1002866 pubmed publisher..Both Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung and trachea; and, although multiple genes ..
- Naiche L, Papaioannou V. Cre activity causes widespread apoptosis and lethal anemia during embryonic development. Genesis. 2007;45:768-75 pubmed..This information will be critical in both evaluating previously published work using cre alleles and in designing future experiments. ..
- Kawakami Y, Marti M, Kawakami H, Itou J, Quach T, Johnson A, et al. Islet1-mediated activation of the ?-catenin pathway is necessary for hindlimb initiation in mice. Development. 2011;138:4465-73 pubmed publisher..Our study identifies Islet1 as a hindlimb-specific transcriptional regulator of initiation, and clarifies the controversy regarding the requirement of ?-catenin for limb initiation...
- Naiche L, Arora R, Kania A, Lewandoski M, Papaioannou V. Identity and fate of Tbx4-expressing cells reveal developmental cell fate decisions in the allantois, limb, and external genitalia. Dev Dyn. 2011;240:2290-300 pubmed publisherT-box gene Tbx4 is critical for the formation of the umbilicus and the initiation of the hindlimb. Previous studies show broad expression in the allantois, hindlimb, lung and proctodeum...
- Lanctot C, Moreau A, Chamberland M, Tremblay M, Drouin J. Hindlimb patterning and mandible development require the Ptx1 gene. Development. 1999;126:1805-10 pubmed..to have retained their molecular identity as assessed by forelimb expression of Tbx5 and by hindlimb expression of Tbx4, even though Tbx4 expression is decreased in Ptx1 null mice...
- Luria V, Krawchuk D, Jessell T, Laufer E, Kania A. Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical control of axonal patterning in the developing limb. Neuron. 2008;60:1039-53 pubmed publisher..The involvement of ephrin:Eph signaling in guiding both sets of motor axons raises the possibility that other signaling systems function primarily to refine or modulate a core Eph signaling program. ..
- Chapman D, Garvey N, Hancock S, Alexiou M, Agulnik S, Gibson Brown J, et al. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Dev Dyn. 1996;206:379-90 pubmed..genes, in contrast to a striking similarity in expression between members of the 2 cognate gene sets, Tbx2/Tbx3 and Tbx4/Tbx5...
- Yang L, Cai C, Lin L, Qyang Y, Chung C, Monteiro R, et al. Isl1Cre reveals a common Bmp pathway in heart and limb development. Development. 2006;133:1575-85 pubmed..Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo. ..
- Naiche L, Papaioannou V. Tbx4 is not required for hindlimb identity or post-bud hindlimb outgrowth. Development. 2007;134:93-103 pubmedb>Tbx4 is a crucial gene in the initiation of hindlimb development and has been reported as a determinant of hindlimb identity and a presumptive direct regulator of Fgf10 in the limb...
- Ouimette J, Jolin M, L honoré A, Gifuni A, Drouin J. Divergent transcriptional activities determine limb identity. Nat Commun. 2010;1:35 pubmed publisher..This programme is modulated by limb-restricted regulators such as hindlimb (HL) transcription factors Pitx1 and Tbx4 and the forelimb (FL) Tbx5...
- Marcil A, Dumontier E, Chamberland M, Camper S, Drouin J. Pitx1 and Pitx2 are required for development of hindlimb buds. Development. 2003;130:45-55 pubmed..Thus, Pitx1 and Pitx2 genes are required for sustained hindlimb bud growth and formation of hindlimbs. ..
- Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, et al. Fgf10 is essential for limb and lung formation. Nat Genet. 1999;21:138-41 pubmed..Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation. ..
- Dobreva M, Lhoest L, Pereira P, Umans L, Camus A, Chuva de Sousa Lopes S, et al. Periostin as a biomarker of the amniotic membrane. Stem Cells Int. 2012;2012:987185 pubmed publisher..In addition, we identify and propose a combination of markers as transcriptional signature for the different extraembryonic tissues in mouse. ..
- Douglas N, Arora R, Chen C, Sauer M, Papaioannou V. Investigating the role of tbx4 in the female germline in mice. Biol Reprod. 2013;89:148 pubmed publisher..b>Tbx4, a member of the T-box family of transcription factors, is expressed in embryonic germ cells and postnatal oocytes ..
- Burns R, Fairbanks T, Sala F, De Langhe S, Mailleux A, Thiery J, et al. Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor 2-IIIb signaling for cecal development in mouse. Dev Biol. 2004;265:61-74 pubmed..Other relevant signaling molecules such as Sonic hedgehog, Wnt2b, and Tbx4 transcripts are found throughout the gut epithelium, including the cecum...
- Cota C, GARCIA GARCIA M. The ENU-induced cetus mutation reveals an essential role of the DNA helicase DDX11 for mesoderm development during early mouse embryogenesis. Dev Dyn. 2012;241:1249-59 pubmed publisher..Studies in yeast and humans have shown requirements for DDX11 in sister chromatid cohesion and DNA repair. In mouse, loss of Ddx11 results in embryonic lethality. However, the developmental defects of Ddx11 mutants are poorly understood...
- Infante C, Mihala A, Park S, Wang J, Johnson K, Lauderdale J, et al. Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes. Dev Cell. 2015;35:107-19 pubmed publisher..In mice, deletion of HLEB, an enhancer of Tbx4, produces defects in hindlimbs and genitalia, establishing the importance of this limb-genital enhancer for ..
- Li D, Sakuma R, Vakili N, Mo R, Puviindran V, Deimling S, et al. Formation of proximal and anterior limb skeleton requires early function of Irx3 and Irx5 and is negatively regulated by Shh signaling. Dev Cell. 2014;29:233-40 pubmed publisher..Our data provide genetic evidence supporting the concept of early specification and progressive determination of anterior limb pattern. ..
- Sgantzis N, Yiakouvaki A, Remboutsika E, Kontoyiannis D. HuR controls lung branching morphogenesis and mesenchymal FGF networks. Dev Biol. 2011;354:267-79 pubmed publisher..key inducer of bud outgrowth and endodermal branching, FGF10 and one of its putative transcriptional regulators, Tbx4. Furthermore, exogenous FGF10 could rescue the branching defect of affected lung buds...
- Pazin D, Gamer L, Cox K, Rosen V. Molecular profiling of synovial joints: use of microarray analysis to identify factors that direct the development of the knee and elbow. Dev Dyn. 2012;241:1816-26 pubmed publisher..The knee is enriched for the hindlimb patterning genes Hoxc9, Hoxc10, and Tbx4 and for Tgfbi, Rspo2, and Sfrp2, factors involved in transforming growth factor-beta/bone morphogenetic protein (..
- Branchfield K, Li R, Lungová V, Verheyden J, McCulley D, Sun X. A three-dimensional study of alveologenesis in mouse lung. Dev Biol. 2016;409:429-41 pubmed publisher..These insights revealed by 3D reconstruction of the septae set the foundation for future investigations of the mechanisms driving normal alveologenesis, as well as causes of alveolar simplification in BPD. ..
- Zuniga A, Quillet R, Perrin Schmitt F, Zeller R. Mouse Twist is required for fibroblast growth factor-mediated epithelial-mesenchymal signalling and cell survival during limb morphogenesis. Mech Dev. 2002;114:51-9 pubmed..Finally, Twist function, most likely by regulating FGF signalling, is required for cell survival as apoptotic cells are detected in posterior and distal limb bud mesenchyme. ..
- Koshiba Takeuchi K, Takeuchi J, Arruda E, Kathiriya I, Mo R, Hui C, et al. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nat Genet. 2006;38:175-83 pubmed..Thus, a positive and negative feed-forward circuit between Tbx5 and Sall4 ensures precise patterning of embryonic limb and heart and provides a unifying mechanism for heart/hand syndromes. ..
- Yokoyama S, Hashimoto M, Shimizu H, Ueno Kudoh H, Uchibe K, Kimura I, et al. Dynamic gene expression of Lin-28 during embryonic development in mouse and chicken. Gene Expr Patterns. 2008;8:155-60 pubmed
- Duboc V, Logan M. Pitx1 is necessary for normal initiation of hindlimb outgrowth through regulation of Tbx4 expression and shapes hindlimb morphologies via targeted growth control. Development. 2011;138:5301-9 pubmed publisher..Pitx1 is also necessary for normal expression of Tbx4, a transcription factor required for normal hindlimb development...
- Yi L, Domyan E, Lewandoski M, Sun X. Fibroblast growth factor 9 signaling inhibits airway smooth muscle differentiation in mouse lung. Dev Dyn. 2009;238:123-37 pubmed publisher..This model also represents our findings on the genetic relationship between FGF9 and sonic hedgehog (SHH) in the establishment of airway SMC pattern. ..
- Marikawa Y, Fujita T, Alarcon V. An enhancer-trap LacZ transgene reveals a distinct expression pattern of Kinesin family 26B in mouse embryos. Dev Genes Evol. 2004;214:64-71 pubmed..5-kb mRNA was the major Kif26B transcript in the embryo, it was absent in many adult tissues. These results imply that KIF26B may play a role in embryogenesis, specifically in the development of limbs, face, and somites. ..
- Hajduk P, Murphy P, Puri P. Mesenchymal expression of Tbx4 gene is not altered in Adriamycin mouse model. Pediatr Surg Int. 2010;26:407-11 pubmed publisher..b>Tbx4 is a member of the T-box family of transcription factor genes, which is reported to play a key role in separation ..
- Jurberg A, Aires R, Varela Lasheras I, Novoa A, Mallo M. Switching axial progenitors from producing trunk to tail tissues in vertebrate embryos. Dev Cell. 2013;25:451-62 pubmed publisher..Our findings provide a perspective to understand the evolution of the vertebrate body plan...
- Nandadasa S, Nelson C, Apte S. ADAMTS9-Mediated Extracellular Matrix Dynamics Regulates Umbilical Cord Vascular Smooth Muscle Differentiation and Rotation. Cell Rep. 2015;11:1519-28 pubmed publisher..In addition, we observed disrupted Shh signaling and perturbed orientation of the mesenchymal primary cilium. Thus, ECM dynamics is a major influence on umbilical vascular SMC fate, with ADAMTS9 acting as its principal mediator. ..
- McCulley D, Wienhold M, Hines E, Hacker T, Rogers A, Pewowaruk R, et al. PBX transcription factors drive pulmonary vascular adaptation to birth. J Clin Invest. 2018;128:655-667 pubmed publisher..More broadly, our findings indicate that neonatal PH can result from perturbation of multiple pathways and suggest that targeting the downstream common effectors may be a more effective treatment for neonatal PH. ..
- Keyte A, Smith K. Developmental origins of precocial forelimbs in marsupial neonates. Development. 2010;137:4283-94 pubmed publisher..Using Tbx5 and Tbx4 as fore- and hindlimb field markers, respectively, we have found that, compared with mouse, both limb fields arise ..
- Snowball J, Ambalavanan M, Whitsett J, Sinner D. Endodermal Wnt signaling is required for tracheal cartilage formation. Dev Biol. 2015;405:56-70 pubmed publisher..Expression of Tbx4, Tbx5, Msx1 and Msx2, known to mediate cartilage and muscle patterning, were decreased in tracheal mesenchyme of ..
- Li M, Li C, Liu Y, Xing Y, Hu L, Borok Z, et al. Mesodermal deletion of transforming growth factor-beta receptor II disrupts lung epithelial morphogenesis: cross-talk between TGF-beta and Sonic hedgehog pathways. J Biol Chem. 2008;283:36257-64 pubmed publisher..To our knowledge, this is the first in vivo evidence for a reciprocal and novel mode of cross-communication between Shh and TGF-beta pathways during embryonic development. ..
- Rakeman A, Anderson K. Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching. Development. 2006;133:3075-83 pubmed..Thus, the Nap1 mutant phenotypes define the crucial roles of Nap1/WAVE-mediated actin regulation in tissue organization and establishment of the body plan of the mammalian embryo. ..
- Khan P, Linkhart B, Simon H. Different regulation of T-box genes Tbx4 and Tbx5 during limb development and limb regeneration. Dev Biol. 2002;250:383-92 pubmedThe T-domain transcription factors Tbx4 and Tbx5 have been implicated, by virtue of their limb-type specific expression, in controlling the identity of vertebrate legs and arms, respectively...
- O Rourke M, Soo K, Behringer R, Hui C, Tam P. Twist plays an essential role in FGF and SHH signal transduction during mouse limb development. Dev Biol. 2002;248:143-56 pubmed..Twist activity is therefore essential for the growth and differentiation of the limb bud tissues as well as regulation of tissue patterning via the modulation of SHH and FGF signal transduction. ..
- Namba T, Sugimoto Y, Hirata M, Hayashi Y, Honda A, Watabe A, et al. Mouse thromboxane A2 receptor: cDNA cloning, expression and northern blot analysis. Biochem Biophys Res Commun. 1992;184:1197-203 pubmed..Northern blot analysis demonstrated that thromboxane A2 receptor mRNA is expressed abundantly in thymus, spleen and lung. ..
- Liao X, Collins M. All-trans retinoic acid-induced ectopic limb and caudal structures: murine strain sensitivities and pathogenesis. Dev Dyn. 2008;237:1553-64 pubmed publisher..Ectopic limbs were hindlimbs (expressing Pitx1 and Tbx4 but not Tbx5), yet they also expressed the predominantly forelimb Hoxb8...
- Nam J, Park E, Turcotte T, Palencia S, Zhan X, Lee J, et al. Mouse R-spondin2 is required for apical ectodermal ridge maintenance in the hindlimb. Dev Biol. 2007;311:124-35 pubmed..Our findings strongly suggest that Rspo2 expression in the AER is required for AER maintenance likely by regulating Wnt/beta-catenin signaling. ..
- Wattler S, Russ A, Evans M, Nehls M. A combined analysis of genomic and primary protein structure defines the phylogenetic relationship of new members if the T-box family. Genomics. 1998;48:24-33 pubmed..We propose a model for the phylogenetic relationships within the gene family that provides a rationale for classifying new T-box genes and facilitates interspecific comparisons. ..
- Cohen D, Green R, Wu M, Beier D. Cloning, tissue-specific expression, gene structure and chromosomal localization of human phosphatidylcholine transfer protein. Biochim Biophys Acta. 1999;1447:265-70 pubmed
- Yi C, Russ A, Brook J. Virtual cloning and physical mapping of a human T-box gene, TBX4. Genomics. 2000;67:92-5 pubmed..b>TBX4, a human member of the Tbx2/3/4/5 subfamily, has been identified and characterized from a high-throughput genomic ..
- Domyan E, Branchfield K, Gibson D, Naiche L, Lewandoski M, Tessier Lavigne M, et al. Roundabout receptors are critical for foregut separation from the body wall. Dev Cell. 2013;24:52-63 pubmed publisher..In humans, genomic lesions containing Robo genes have been documented in CDH. Our findings suggest that separation of the foregut from the body wall is genetically controlled and that defects in this event may contribute to CDH. ..
- Zhang L, Chase M, Shen R. Molecular cloning and expression of murine thromboxane synthase. Biochem Biophys Res Commun. 1993;194:741-8 pubmed
- Suzuki K, Adachi Y, Numata T, Nakada S, Yanagita M, Nakagata N, et al. Reduced BMP signaling results in hindlimb fusion with lethal pelvic/urogenital organ aplasia: a new mouse model of sirenomelia. PLoS ONE. 2012;7:e43453 pubmed publisher..Our study offers new insights into the pathogenesis of sirenomelia. ..
- Narkis G, Tzchori I, Cohen T, Holtz A, Wier E, Westphal H. Isl1 and Ldb co-regulators of transcription are essential early determinants of mouse limb development. Dev Dyn. 2012;241:787-91 pubmed publisher..Thus, Isl1 and the Ldb co-regulators of transcription are essential early determinants of mouse limb development. Isl1/Ldb complexes regulate Fgf10 to orchestrate the earliest stages of hindlimb formation. ..
- Rawnsley D, Xiao J, Lee J, Liu X, Mericko Ishizuka P, Kumar V, et al. The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development. J Biol Chem. 2013;288:24429-40 pubmed publisher..Whether ATOH8 modulates GATA-FOG function at other sites or in more subtle ways in mammals is not yet known...
- Carraro G, Shrestha A, Rostkovius J, Contreras A, Chao C, El Agha E, et al. miR-142-3p balances proliferation and differentiation of mesenchymal cells during lung development. Development. 2014;141:1272-81 pubmed publisher..These findings show that in the embryonic lung mesenchyme, the microRNA machinery modulates the level of WNT signaling, adding an extra layer of control in the feedback loop between FGFR2C and ?-catenin-mediated WNT signaling. ..
- Luria V, Laufer E. Lateral motor column axons execute a ternary trajectory choice between limb and body tissues. Neural Dev. 2007;2:13 pubmed..When making this choice, medial and lateral LMC axons exhibit different and asymmetric relative preferences for these three trajectories. These data redefine the LMC as a motor column that innervates both limb and body tissues. ..
- Voss A, Vanyai H, Collin C, Dixon M, McLennan T, Sheikh B, et al. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Dev Cell. 2012;23:652-63 pubmed publisher..Our data reveal a molecular mechanism for a specific chromatin modification of the Tbx1 locus intersecting with an environmental determinant, modeling variability in DiGeorge syndrome. ..
- 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..5 days postcoitus, indicating that the continued expression of Tbx6 is directly or indirectly dependent upon Brachyury expression. ..
- Agulnik S, Garvey N, Hancock S, Ruvinsky I, Chapman D, Agulnik I, et al. Evolution of mouse T-box genes by tandem duplication and cluster dispersion. Genetics. 1996;144:249-54 pubmed..Here, we report the discovery of three new members of the mouse T-box gene family, named Tbx4, Tbx5, and Tbx6...
- Xie T, Liang J, Liu N, Huan C, Zhang Y, Liu W, et al. Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis. J Clin Invest. 2016;126:3063-79 pubmed publisher..gene expression transgenic reporting methods to analyze the early embryonic transcription factor T-box gene 4 (TBX4), and determined that TBX4-lineage mesenchymal progenitors are the predominant source of myofibroblasts in injured ..
- Boucherat O, Landry Truchon K, Aoidi R, Houde N, Nadeau V, Charron J, et al. Lung development requires an active ERK/MAPK pathway in the lung mesenchyme. Dev Dyn. 2017;246:72-82 pubmed publisher..To address the role of the ERK/MAPK pathway in lung mesenchyme in absence of kyphosis and omphalocele, we used the Tbx4Cre deleter mouse line, which acts specifically in lung mesenchyme...
- Shibata M, GARCIA GARCIA M. The mouse KRAB zinc-finger protein CHATO is required in embryonic-derived tissues to control yolk sac and placenta morphogenesis. Dev Biol. 2011;349:331-41 pubmed publisher..Our results support previously undescribed roles of the extraembryonic mesoderm in yolk sac morphogenesis and in the closure of the ectoplacental cavity and identify a novel role of ZFP568 in the development of extraembryonic tissues...
- Garrido Allepuz C, González Lamuño D, Ros M. Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations. PLoS ONE. 2012;7:e44962 pubmed publisher..Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia. ..
- Ruvinsky I, Gibson Brown J. Genetic and developmental bases of serial homology in vertebrate limb evolution. Development. 2000;127:5233-44 pubmed
- Liberatore C, Searcy Schrick R, Yutzey K. Ventricular expression of tbx5 inhibits normal heart chamber development. Dev Biol. 2000;223:169-80 pubmed..These studies provide direct evidence for an essential role for tbx5 in early heart morphogenesis and chamber-specific gene expression. ..
- Turcatel G, Rubin N, Menke D, Martin G, Shi W, Warburton D. Lung mesenchymal expression of Sox9 plays a critical role in tracheal development. BMC Biol. 2013;11:117 pubmed publisher..Sox9 is expressed in both distal lung epithelium and proximal lung mesenchyme. Here, we investigated the effect of lung mesenchyme-specific inducible deletion of Sox9 during murine lung development...