Genomes and Genes
Gene Symbol: tbx5a
Description: T-box 5a
Alias: hst, tbx5, tbx5.1, T-box transcription factor TBX5-A, T-box gene 5, T-box gene 5.1, T-box protein 5, T-box transcription factor TBX5, heartstrings
- Qu X, Jia H, Garrity D, Tompkins K, Batts L, Appel B, et al. Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish. Dev Biol. 2008;317:486-96 pubmed publisher..This constellation of ndrg4 cardiac defects phenocopies those seen in mutant hearts of heartstrings (hst), the tbx5 loss-of-function mutants in zebrafish...
- Harvey S, Logan M. sall4 acts downstream of tbx5 and is required for pectoral fin outgrowth. Development. 2006;133:1165-73 pubmed..Mutations in the T-box transcription factor TBX5 cause Holt-Oram syndrome (HOS), which results in forelimb and heart defects...
- Nakayama Y, Miyake A, Nakagawa Y, Mido T, Yoshikawa M, Konishi M, et al. Fgf19 is required for zebrafish lens and retina development. Dev Biol. 2008;313:752-66 pubmed..Knockdown of Fgf19 also caused incorrect axon pathfinding. The present findings indicate that Fgf19 positively regulates the patterning and growth of the retina, and the differentiation and growth of the lens in zebrafish. ..
- Chiavacci E, Dolfi L, Verduci L, Meghini F, Gestri G, Evangelista A, et al. MicroRNA 218 mediates the effects of Tbx5a over-expression on zebrafish heart development. PLoS ONE. 2012;7:e50536 pubmed publisherb>tbx5, a member of the T-box gene family, encodes one of the key transcription factors mediating vertebrate heart development...
- Albalat R, Baquero M, Minguillon C. Identification and characterisation of the developmental expression pattern of tbx5b, a novel tbx5 gene in zebrafish. Gene Expr Patterns. 2010;10:24-30 pubmed publisher..has retained the eye and heart expression, partially overlapping with that of its paralogue, now referred to as tbx5a. Functional redundancy of tbx5a and tbx5b in the eye and heart would therefore explain the mild phenotypes ..
- Ng J, Kawakami Y, Buscher D, Raya A, Itoh T, Koth C, et al. The limb identity gene Tbx5 promotes limb initiation by interacting with Wnt2b and Fgf10. Development. 2002;129:5161-70 pubmed..Combining mutant analyses with gain- and loss-of-function approaches in zebrafish and chick embryos, we show that Tbx5, in addition to its role governing forelimb identity, is both necessary and sufficient for limb outgrowth...
- Gibert Y, Gajewski A, Meyer A, Begemann G. Induction and prepatterning of the zebrafish pectoral fin bud requires axial retinoic acid signaling. Development. 2006;133:2649-59 pubmed..Thus, RA signaling from flanking somites plays a dual early role in the condensing limb bud mesenchyme. ..
- French C, Erickson T, Callander D, Berry K, Koss R, Hagey D, et al. Pbx homeodomain proteins pattern both the zebrafish retina and tectum. BMC Dev Biol. 2007;7:85 pubmed..These data define a novel role for Pbx in patterning the vertebrate retina and tectum in a manner required for proper retinal ganglion cell axon outgrowth. ..
- McMahon C, Gestri G, Wilson S, Link B. Lmx1b is essential for survival of periocular mesenchymal cells and influences Fgf-mediated retinal patterning in zebrafish. Dev Biol. 2009;332:287-98 pubmed publisher..Overall, we propose zebrafish lmx1b.1 and lmx1b.2 promote the survival of periocular mesenchymal cells that influence multiple signaling events required for proper ocular development. ..
- Picker A, Brand M. Fgf signals from a novel signaling center determine axial patterning of the prospective neural retina. Development. 2005;132:4951-62 pubmed
- Waskiewicz A, Rikhof H, Hernandez R, Moens C. Zebrafish Meis functions to stabilize Pbx proteins and regulate hindbrain patterning. Development. 2001;128:4139-51 pubmed..Our results define two functions of Meis during zebrafish hindbrain segmentation: that of a DNA-binding partner of Pbx proteins, and that of a post-transcriptional regulator of Pbx protein levels. ..
- Lu J, Lu J, Choo S, Li Y, Yeh H, Shiue J, et al. Cascade effect of cardiac myogenesis gene expression during cardiac looping in tbx5 knockdown zebrafish embryos. J Biomed Sci. 2008;15:779-87 pubmed publisherZebrafish tbx5 expresses in the heart, pectoral fins and eyes of zebrafish during embryonic development...
- Szeto D, Griffin K, Kimelman D. HrT is required for cardiovascular development in zebrafish. Development. 2002;129:5093-101 pubmed..In particular, we found that the loss of hrT function led to a dramatic upregulation of tbx5, a gene required for normal heart morphogenesis...
- Kruse Bend R, Rosenthal J, Quist T, Veien E, Fuhrmann S, Dorsky R, et al. Extraocular ectoderm triggers dorsal retinal fate during optic vesicle evagination in zebrafish. Dev Biol. 2012;371:57-65 pubmed publisher..We find that bmp2b is involved in dorsal retina initiation, acting upstream of gdf6a. Together, this work has identified the nature and source of extraocular signals required to pattern the dorsal retina. ..
- Parrie L, Renfrew E, Wal A, Mueller R, Garrity D. Zebrafish tbx5 paralogs demonstrate independent essential requirements in cardiac and pectoral fin development. Dev Dyn. 2013;242:485-502 pubmed publisher..Homozygous mutation of zebrafish tbx5a leads to lethal defects in cardiac looping morphogenesis, blocks pectoral fin initiation, and impairs outgrowth...
- Mercader N, Fischer S, Neumann C. Prdm1 acts downstream of a sequential RA, Wnt and Fgf signaling cascade during zebrafish forelimb induction. Development. 2006;133:2805-15 pubmed..b>tbx5 is the earliest gene expressed in the limb bud mesenchyme...
- Gross J, Dowling J. Tbx2b is essential for neuronal differentiation along the dorsal/ventral axis of the zebrafish retina. Proc Natl Acad Sci U S A. 2005;102:4371-6 pubmed..Combined, these observations suggest that the cellular mechanisms regulating neuronal differentiation within the retina are asymmetric about the dorsal/ventral axis and that Tbx2b mediates this process within the dorsal retina. ..
- Ahn D, Kourakis M, Rohde L, Silver L, Ho R. T-box gene tbx5 is essential for formation of the pectoral limb bud. Nature. 2002;417:754-8 pubmedThe T-box genes Tbx4 and Tbx5 have been shown to have key functions in the specification of the identity of the vertebrate forelimb (Tbx5) and hindlimb (Tbx4)...
- Camarata T, Krcmery J, Snyder D, Park S, Topczewski J, Simon H. Pdlim7 (LMP4) regulation of Tbx5 specifies zebrafish heart atrio-ventricular boundary and valve formation. Dev Biol. 2010;337:233-45 pubmed publisher..Knock-down of Pdlim7 results in a non-looped heart, strikingly reminiscent of the tbx5 heartstrings mutant phenotype...
- Chi N, Shaw R, De Val S, Kang G, Jan L, Black B, et al. Foxn4 directly regulates tbx2b expression and atrioventricular canal formation. Genes Dev. 2008;22:734-9 pubmed publisher..sli/foxn4 is expressed in the AV canal, and its encoded product binds to a highly conserved tbx2 enhancer domain that contains Foxn4- and T-box-binding sites, both necessary to regulate tbx2b expression in the AV canal. ..
- Garrity D, Childs S, Fishman M. The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome. Development. 2002;129:4635-45 pubmed..In a screen for mutations affecting zebrafish cardiac function, we isolated the recessive lethal mutant heartstrings, which lacks pectoral fins and exhibits severe cardiac dysfunction, beginning with a slow heart rate and ..
- Fischer S, Draper B, Neumann C. The zebrafish fgf24 mutant identifies an additional level of Fgf signaling involved in vertebrate forelimb initiation. Development. 2003;130:3515-24 pubmed..mesoderm by a cascade of genes, including members of the Fgf and Wnt families, as well as the transcription factor tbx5. Fgf8, which is expressed in the intermediate mesoderm, is thought to initiate forelimb formation by activating ..
- Takeuchi J, Lou X, Alexander J, Sugizaki H, Delgado Olguin P, Holloway A, et al. Chromatin remodelling complex dosage modulates transcription factor function in heart development. Nat Commun. 2011;2:187 pubmed publisher..Disrupting the balance between Brg1 and disease-causing cardiac transcription factors, including Tbx5, Tbx20 and Nkx2-5, causes severe cardiac anomalies, revealing an essential allelic balance between Brg1 and these ..
- Rothschild S, Easley C, Francescatto L, Lister J, Garrity D, Tombes R. Tbx5-mediated expression of Ca(2+)/calmodulin-dependent protein kinase II is necessary for zebrafish cardiac and pectoral fin morphogenesis. Dev Biol. 2009;330:175-84 pubmed publisher..Similarly, zebrafish tbx5 morphants and mutants (heartstrings; hst) lack pectoral fins and exhibit a persistently elongated heart that does not undergo chamber looping...
- Lu J, Tsai T, Choo S, Yeh S, Tang R, Yang A, et al. Induction of apoptosis and inhibition of cell growth by tbx5 knockdown contribute to dysmorphogenesis in Zebrafish embryos. J Biomed Sci. 2011;18:73 pubmed publisherThe tbx5 mutation in human causes Holt-Oram syndrome, an autosomal dominant condition characterized by a familial history of congenital heart defects and preaxial radial upper-limb defects...
- Ghosh T, Song F, Packham E, Buxton S, Robinson T, Ronksley J, et al. Physical interaction between TBX5 and MEF2C is required for early heart development. Mol Cell Biol. 2009;29:2205-18 pubmed publisherb>TBX5 is a transcription factor which plays important roles in the development of the heart and upper limbs. Mutations in this gene produce the inherited disorder Holt-Oram syndrome...
- Smith K, Lagendijk A, Courtney A, Chen H, Paterson S, Hogan B, et al. Transmembrane protein 2 (Tmem2) is required to regionally restrict atrioventricular canal boundary and endocardial cushion development. Development. 2011;138:4193-8 pubmed publisher..Finally, we show that immature AVC expansion in wkm mutants is rescued by depleting Bmp4, indicating that Tmem2 restricts bmp4 expression to delimit the AVC primordium during cardiac development. ..
- McIntyre J, Edmunds R, Redig M, Mudrock E, Davis J, Incardona J, et al. Confirmation of Stormwater Bioretention Treatment Effectiveness Using Molecular Indicators of Cardiovascular Toxicity in Developing Fish. Environ Sci Technol. 2016;50:1561-9 pubmed publisher..Molecular markers were more sensitive than visible toxicity indicators, and several cardiac-related genes show promise as novel tools for evaluating the effectiveness of evolving stormwater mitigation strategies. ..
- Wang F, Liu D, Zhang R, Yu L, Zhao J, Yang X, et al. A TBX5 3'UTR variant increases the risk of congenital heart disease in the Han Chinese population. Cell Discov. 2017;3:17026 pubmed publisherb>TBX5 is a vital transcription factor involved in cardiac development in a dosage-dependent manner...
- OcaÃ±a O, Coskun H, MinguillÃ³n C, Murawala P, Tanaka E, GalcerÃ¡n J, et al. A right-handed signalling pathway drives heart looping in vertebrates. Nature. 2017;549:86-90 pubmed publisher..Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates. ..
- Caputo L, Witzel H, Kolovos P, Cheedipudi S, Looso M, Mylona A, et al. The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors. Cell Stem Cell. 2015;17:287-99 pubmed publisher..In conclusion, the Isl1/Ldb1 complex orchestrates a network forÂ heart-specific transcriptional regulation and coordination in three-dimensional space during cardiogenesis. ..
- Peterkin T, Gibson A, Patient R. Redundancy and evolution of GATA factor requirements in development of the myocardium. Dev Biol. 2007;311:623-35 pubmed
- Samuel A, Rubinstein A, Azar T, Ben Moshe Livne Z, Kim S, Inbal A. Six3 regulates optic nerve development via multiple mechanisms. Sci Rep. 2016;6:20267 pubmed publisher..Hence, the new zebrafish model for Six3 loss of function furthers our understanding of the mechanisms governing optic nerve development and Six3-mediated eye and forebrain malformations. ..
- Jiang L, Li K, Lin Q, Ren J, He Z, Li H, et al. Gambogic acid causes fin developmental defect in zebrafish embryo partially via retinoic acid signaling. Reprod Toxicol. 2016;63:161-8 pubmed publisher..These results indicate the potential teratogenicity of GA and provide evidence for a caution in its future clinic use. ..
- Xiao Y, Gao M, Gao L, Zhao Y, Hong Q, Li Z, et al. Directed Differentiation of Zebrafish Pluripotent Embryonic Cells to Functional Cardiomyocytes. Stem Cell Reports. 2016;7:370-382 pubmed publisher..The technology provides a new platform for the study of heart development and regeneration, in addition to drug discovery, disease modeling, and assessment of cardiotoxic agents. ..
- Neto A, Mercader N, Gomez Skarmeta J. The Osr1 and Osr2 genes act in the pronephric anlage downstream of retinoic acid signaling and upstream of Wnt2b to maintain pectoral fin development. Development. 2012;139:301-11 pubmed publisher..Reduction of zebrafish Osr function impairs fin development by the failure of tbx5a maintenance in the developing pectoral fin bud...
- Sun G, Liu K. Developmental toxicity and cardiac effects of butyl benzyl phthalate in zebrafish embryos. Aquat Toxicol. 2017;192:165-170 pubmed publisher..BBP could induce developmental toxicity, with adverse effects on the heart development in zebrafish embryos, and alter the expression of genes related to heart development. ..
- Lepilina A, Coon A, Kikuchi K, Holdway J, Roberts R, Burns C, et al. A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell. 2006;127:607-19 pubmed..Our findings reveal injury responses by myocardial and epicardial tissues that collaborate in an Fgf-dependent manner to achieve cardiac regeneration...
- Rottbauer W, Just S, Wessels G, Trano N, Most P, Katus H, et al. VEGF-PLCgamma1 pathway controls cardiac contractility in the embryonic heart. Genes Dev. 2005;19:1624-34 pubmed..Thus, the muscle of the heart uses the VEGF-PLCgamma1 cascade to control the strength of the heart beat. We speculate that this paracrine system may contribute to normal and pathological regulation of cardiac contractility. ..
- Sultana N, Nag K, Hoshijima K, Laird D, Kawakami A, Hirose S. Zebrafish early cardiac connexin, Cx36.7/Ecx, regulates myofibril orientation and heart morphogenesis by establishing Nkx2.5 expression. Proc Natl Acad Sci U S A. 2008;105:4763-8 pubmed publisher..5 was down-regulated in the ftk heart despite the normal expression of gata4 and tbx5, suggesting a common mechanism for the occurrence of ftk phenotype and CHD...
- Huynen L, Suzuki T, Ogura T, Watanabe Y, Millar C, Hofreiter M, et al. Reconstruction and in vivo analysis of the extinct tbx5 gene from ancient wingless moa (Aves: Dinornithiformes). BMC Evol Biol. 2014;14:75 pubmed publisherThe forelimb-specific gene tbx5 is highly conserved and essential for the development of forelimbs in zebrafish, mice, and humans...
- Cardozo M, Sánchez Arrones L, Sandonìs A, Sánchez Camacho C, Gestri G, Wilson S, et al. Cdon acts as a Hedgehog decoy receptor during proximal-distal patterning of the optic vesicle. Nat Commun. 2014;5:4272 pubmed publisher..This Ptc-independent function protects the retinal primordium from Hh activity, defines the stalk/retina boundary and thus the correct proximo-distal patterning of the eye. ..
- Wang X, Yu Q, Wu Q, Bu Y, Chang N, Yan S, et al. Genetic interaction between pku300 and fbn2b controls endocardial cell proliferation and valve development in zebrafish. J Cell Sci. 2013;126:1381-91 pubmed publisher..We conclude that pku300 and fbn2b represent the few genes capable of regulating endocardial cell proliferation and signaling in zebrafish cardiac valve development. ..
- Naylor R, Skvarca L, Thisse C, Thisse B, Hukriede N, Davidson A. BMP and retinoic acid regulate anterior-posterior patterning of the non-axial mesoderm across the dorsal-ventral axis. Nat Commun. 2016;7:12197 pubmed publisher..This work clarifies our understanding of vertebrate axis orientation and establishes a new paradigm for how the kidney and other mesodermal derivatives arise during embryogenesis. ..
- Wang Y, Qian L, Yu Z, Jiang Q, Dong Y, Liu X, et al. Requirements of myocyte-specific enhancer factor 2A in zebrafish cardiac contractility. FEBS Lett. 2005;579:4843-50 pubmed..Dysregulation of cardiac genes in MEF2A morphants suggests that sarcomere assembly disturbances account for the cardiac contractile deficiency. Our studies suggested that MEF2A is essential in cardiac contractility. ..
- Novikov N, Evans T. Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling. Development. 2013;140:3787-98 pubmed publisher..Tmem88a is a novel component of the regulatory mechanism controlling the second phase of biphasic WNT activity essential for embryonic cardiogenesis. ..
- Wang Y, Qian L, Liu D, Yao L, Jiang Q, Yu Z, et al. Bone morphogenetic protein-2 acts upstream of myocyte-specific enhancer factor 2a to control embryonic cardiac contractility. Cardiovasc Res. 2007;74:290-303 pubmed
- Hong Z, Zhang Y, Zuo Z, Zhu R, Gao Y. Influences of domoic Acid exposure on cardiac development and the expression of cardiovascular relative genes in zebrafish (Daniorerio) embryos. J Biochem Mol Toxicol. 2015;29:254-60 pubmed publisher..We found that DA exposure not only disrupted normal cardiac development but also altered the expression of some cardiac development correlated genes and calcium ion channels, such as Anf, Bnp, Atp2a2a, Atp2a2b, Ncx1h, Ryr2b, and Tbx5.
- 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...
- Ma H, Blake T, Chitnis A, Liu P, Balla T. Crucial role of phosphatidylinositol 4-kinase IIIalpha in development of zebrafish pectoral fin is linked to phosphoinositide 3-kinase and FGF signaling. J Cell Sci. 2009;122:4303-10 pubmed publisher..Our results identify Pik4a as an upstream partner of PI3Ks in the signaling cascade orchestrated by FGF receptors with a prominent role in forelimb development. ..
- Boisset G, Schorderet D. Zebrafish hmx1 promotes retinogenesis. Exp Eye Res. 2012;105:34-42 pubmed publisher..However, the key patterning genes tested so far were not regulated by hmx1. Altogether, these results suggest an important role for hmx1 in retinogenesis. ..
- Zhang Y, Wang C, Huang L, Chen R, Chen Y, Zuo Z. Low-level pyrene exposure causes cardiac toxicity in zebrafish (Danio rerio) embryos. Aquat Toxicol. 2012;114-115:119-24 pubmed publisher..Taken together, these data indicated that embryonic exposure of zebrafish to low-level environmental pyrene disrupt normal cardiac development and alter expression of defective cardiac differentiation related genes. ..
- Choudhry P, Trede N. DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart looping and differentiation. PLoS ONE. 2013;8:e58145 pubmed publisher..This is the first study linking tbx1 and non-canonical Wnt signaling and extends our understanding of DGS and heart development. ..
- Mao Q, Stinnett H, Ho R. Asymmetric cell convergence-driven zebrafish fin bud initiation and pre-pattern requires Tbx5a control of a mesenchymal Fgf signal. Development. 2015;142:4329-39 pubmed publisher..Combining single-cell fate mapping and three-dimensional cell tracking in the zebrafish, we describe a Tbx5a-dependent cell convergence pattern that is both asymmetric and topological within the fin-field lateral plate ..
- Adachi N, Robinson M, Goolsbee A, Shubin N. Regulatory evolution of Tbx5 and the origin of paired appendages. Proc Natl Acad Sci U S A. 2016;113:10115-20 pubmed publisher..activity is evolutionarily conserved among jawed vertebrates and is able to rescue the finless phenotype of tbx5a mutant zebrafish...
- Ryan K, Chin A. T-box genes and cardiac development. Birth Defects Res C Embryo Today. 2003;69:25-37 pubmed..Over the last 5 years, mutations in TBX1 and TBX5 have been implicated in two human disorders with haplo-insufficient cardiovascular phenotypes, DiGeorge/..
- He X, Yan Y, Eberhart J, Herpin A, Wagner T, Schartl M, et al. miR-196 regulates axial patterning and pectoral appendage initiation. Dev Biol. 2011;357:463-77 pubmed publisher..These results show that a Hox cluster microRNA modulates development of axial patterning similar to nearby protein-coding Hox genes, and acts on appendicular patterning at least in part by modulating retinoic acid signaling. ..
- Lam P, Kamei C, Mangos S, Mudumana S, Liu Y, Drummond I. odd-skipped related 2 is required for fin chondrogenesis in zebrafish. Dev Dyn. 2013;242:1284-92 pubmed publisher..The zebrafish odd-skipped related 2 gene regulates sox9a and col2a1 expression in chondrocyte development and is specifically required for zebrafish fin morphogenesis. ..
- Koudijs M, den Broeder M, Groot E, van Eeden F. Genetic analysis of the two zebrafish patched homologues identifies novel roles for the hedgehog signaling pathway. BMC Dev Biol. 2008;8:15 pubmed publisher..Additionally, these mutants will provide a useful system to further investigate the consequences of constitutively activated Hh signaling during vertebrate development. ..
- Tong X, Zu Y, Li Z, Li W, Ying L, Yang J, et al. Kctd10 regulates heart morphogenesis by repressing the transcriptional activity of Tbx5a in zebrafish. Nat Commun. 2014;5:3153 pubmed publisherThe T-box transcription factor Tbx5 (Tbx5a in zebrafish) plays a crucial role in the formation of cardiac chambers in a dose-dependent manner. Its deregulation leads to congenital heart disease...
- Lee B, Roy S. Blimp-1 is an essential component of the genetic program controlling development of the pectoral limb bud. Dev Biol. 2006;300:623-34 pubmed..We present evidence that blimp-1 functions downstream of tbx5 and fgf24 and therefore is not required for the initial specification of the fin bud primordia...
- Walton R, Bruce A, Olivey H, Najib K, Johnson V, Earley J, et al. Fog1 is required for cardiac looping in zebrafish. Dev Biol. 2006;289:482-93 pubmed..Taken together, these results demonstrate the importance of FOG proteins for zebrafish cardiac development and suggest a previously unappreciated role for FOG proteins in heart looping that is dependent on the FOG repression motif. ..
- Ebert A, Childs S, Hehr C, Cechmanek P, McFarlane S. Sema6a and Plxna2 mediate spatially regulated repulsion within the developing eye to promote eye vesicle cohesion. Development. 2014;141:2473-82 pubmed publisher..We propose a novel, tissue-autonomous mechanism of organ cohesion, with neutralization of repulsion suggested as a means to promote interactions between cells within a tissue domain. ..
- Zhao Y, Yang Z, Phelan J, Wheeler D, Lin S, McCabe E. Zebrafish dax1 is required for development of the interrenal organ, the adrenal cortex equivalent. Mol Endocrinol. 2006;20:2630-40 pubmed..Based on these results, we propose that dax1 is the mammalian DAX1 ortholog, functions downstream of ff1b in the regulatory cascades, and is required for normal development and function of the zebrafish interrenal organ...