<i>Tbx1</i>is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer

Yamagishi, Hiroyuki; Maeda, Jun; Hu, Tonghuan; McAnally, John; Conway, Simon J.; Kume, Tsutomu; Meyers, Erik N.; Yamagishi, Chihiro; Srivastava, Deepak

doi:10.1101/gad.1048903

Cited by 248 publications

(232 citation statements)

References 49 publications

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“…Because Shh and Foxa2 have been shown to be required for tissue specific Tbx1 expression in the pharyngeal endoderm and head mesenchyme (Yamagishi et al, 2003), we examined their expression after the implantation of RA-beads. Neither Shh nor Foxa2 was down-regulated in the pharyngeal endoderm or head mesenchyme, and two further pieces of evidence suggest that it is unlikely that the RA repression of Tbx1 in pharyngeal endoderm is mediated by a decrease in expression of Shh or Foxa2.…”

Section: Discussionmentioning

confidence: 99%

“…The program predicted two RAREs in a region 600 bp upstream of Tbx1 in human and rat, and one in mouse. Whether these sites are of biological significance remains to be seen, because previous studies have demonstrated that some Tbx1 control elements and evolutionary conserved sequences are located many kilobases from the coding sequence (Yamagishi et al, 2003;Brown et al, 2004). Thus, dissection of the sites responsible for RA-mediated repression of Tbx1 could be quite difficult but might be achieved through manipulation of BACs (recombineering) (Testa et al, 2003) to produce the many reporter constructs likely to be required.…”

Section: Discussionmentioning

confidence: 99%

“…Experiments by Yamagishi et al (2003) have shown that Tbx1 can be up-regulated by Shh acting by means of Fox-binding sites in the Tbx1 promoter sequences. We therefore examined the expression of these two genes in embryos grafted with RA beads to establish if the repressive effect of RA was achieved by a decline in either Shh or Foxa2 expression.…”

Section: Exogenous Retinoic Acid Does Not Alter Pharyngeal Shh or Foxmentioning

confidence: 99%

“…Shh already has been demonstrated to induce Tbx1 expression (Garg et al, 2001;Yamagishi et al, 2003), but there remain several other potential candidates that may regulate Tbx1. One of these is retinoic acid (RA), well known as a signaling molecule required for normal development.…”

Section: Introductionmentioning

confidence: 99%

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Retinoic acid down‐regulates Tbx1 expression in vivo and in vitro

Roberts¹,

Ivins²,

James³

et al. 2005

Developmental Dynamics

105

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Both Tbx1 and retinoic acid (RA) are key players in embryonic pharyngeal development; loss of Tbx1 produces DiGeorge syndrome-like phenotypes in mouse models as does disruption of retinoic acid homeostasis. We have demonstrated that perturbation of retinoic acid levels in the avian embryo produces altered Tbx1 expression. In vitamin A-deficient quails, which lack endogenous retinoic acid, Tbx1 expression patterns were disrupted early in development and expression was subsequently lost in all tissues. "Gain-of-function" experiments where RA-soaked beads were grafted into the pharyngeal region produced localized down-regulation of Tbx1 expression. In these embryos, analysis of Shh and Foxa2, upstream control factors for Tbx1, suggested that the effect of RA was independent of this regulatory pathway. Real-time polymerase chain reaction analysis of retinoic acid-treated P19 cells showed a dosedependent repression of Tbx1 by retinoic acid. Repression of Tbx1 transcript levels was first evident after 8 -12 hr in culture in the presence of retinoic acid, and to achieve the highest levels of repression, de novo protein synthesis was required. Developmental Dynamics 232:928 -938, 2005.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Exogenous Retinoic Acid Does Not Alter Pharyngeal Shh or Foxmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Retinoic acid down‐regulates Tbx1 expression in vivo and in vitro

Roberts¹,

Ivins²,

James³

et al. 2005

Developmental Dynamics

105

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“…7 Commonly, the clinical phenotype of individuals with GATA6 mutations involves the OFT, but is distinct from that of DiGeorge/22q11.2 deletion syndrome and, rather, manifests as non-syndromic CHD. To date, no molecular link has been demonstrated between GATA6 and TBX1, 8,9 however, a recent study showed that the expression of Sema3c in the OFT was downregulated in mouse embryos deficient for Tbx1, 10 suggesting that GATA6 may share, at least in part, a common molecular pathway with TBX1 during OFT development.…”

mentioning

confidence: 99%

GATA transcription factors in congenital heart defects: A Commentary on a novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect

Kodo

Yamagishi

2010

J Hum Genet

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C ongenital heart defects (CHDs) occur in nearly 1% of all live births and are the major cause of infant mortality and morbidity. In addition, about 3 per every 1000 live births will require some intervention during the first year of life. 1 Despite its clinical importance, the underlying genetic etiology of most CHD remains unknown. Previous studies succeeded in revealing genetic causes of some syndromic or familial CHD, however, there are limited numbers of such cases, and it is still difficult to approach the etiology of the majority of CHD, that manifest non-syndromic and non-familial phenotype, because of their multi-factorial nature.In this issue, Lin et al. report on a novel mutation of a gene encoding a transcription factor, GATA6, as a possible cause of CHD. 2 The authors screened 270 individuals with non-syndromic CHD for the GATA6 gene by direct sequencing, and identified a missense mutation (S184N) in three individuals, one with tetralogy of Fallot and the others with atrial septal defect. Although the incomplete penetrance of the phenotype by this mutation was observed, the mutation was not found in 500 ethnically matched healthy controls. And their subsequent biological analysis revealed the decreased transcriptional activity of GATA6 with the S184N mutation for the gene regulation of several important cardiac factors, suggesting that the GATA6 S184N mutation may have an important role in the pathogenesis of CHD.The first identification of disease-associated mutations of GATA6 in CHD was originally reported by us. 3 We screened mutations of cardiac transcription factors in patients with selected non-syndromic CHD, namely persistent truncus arteriosus, representing the most severe cardiac outflow tract (OFT) defects. Two different GATA6 mutations were identified in two probands, but not in 182 unrelated controls with no CHD. Our subsequent biological analyses revealed that genes encoding the neurovascular guiding molecule semaphorin 3C and its receptor plexin A2 were directly regulated by GATA6, and both GATA6 mutant proteins failed to transactivate these genes. Transgenic analysis further suggested that the expression of semaphorin 3C and plexin A2 in the OFT was dependent on GATA transcription factors during the heart development. Together, our data implicate mutations in GATA6 as novel genetic causes of CHD involving the OFT development, as a result of the disruption of the direct regulation of semaphorin-plexin signaling. Another recent study by Maitra et al. showed two novel sequence variations in GATA6 (A178V and L198V) from the screening of 310 individuals with CHD. 4 These variants were identified in two individuals, one with tetralogy of Fallot and another with atrioventricular septal defect, but not in 288 ethnically matched healthy controls. Biochemical analysis demonstrated that the GATA6 A178V mutant protein resulted in increased transactivation ability for cardiac genes compared with the wildtype. Our first report and subsequent reports by Maitra et al. 4 and Lin et al. 2 in this issue...

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22q11 Deletion Syndrome: A Role for Tbx1 in Pharynx and Cardiovascular Development

Calmont¹,

Scambler²

2010

Encyclopedia of Life Sciences

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DiGeorge and velocardiofacial syndromes result from a chromosomal deletion involving proximal chromosome 22 and affected individuals commonly present with congenital heart defects, feeding problems, speech delay and learning problems. Psychiatric illness may present later in life. Mutation analysis and creation of mouse models which mimic the human disorder have identified that the Tbx1 (T‐box 1) transcription factor is the major dosage‐sensitive gene in the deletion region and have allowed exploration of the underlying developmental pathways and signalling networks disrupted in these syndromes. Of particular importance in this regard are Fgf (fibroblast growth factor) and retinoic acid signalling. Tbx1 is in genetic epistasis with loci encoding several transcription factors and signalling molecules, providing some rationale for the very variable clinical presentation. Gain‐of‐function, or duplications containing Tbx1 , is also associated with heart defect. Key Concepts: The presence of a dominant phenotype secondary to gene hemizygosity is called haploinsufficiency. Genetic epistasis is the phenomenon where the effects of one gene are modified by one or several other genes, which are called modifier genes. Each pharyngeal arch surrounds an arch artery that connects the heart, by means of the aortic sac, to the dorsal aortae. The neural crest is a pluripotent embryonic neuroectodermal cell population that migrates extensively and differentiates into diverse structures such as the face, neck, heart, adrenal gland, peripheral nervous system and skin. Low copy number repeat are 1–400 kb blocks of genomic sequence that are duplicated in one or more locations on a chromosome and can act as substrates for aberrant recombination events.

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Tbx1is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer

Cited by 248 publications

References 49 publications

Retinoic acid down‐regulates Tbx1 expression in vivo and in vitro

Retinoic acid down‐regulates Tbx1 expression in vivo and in vitro

GATA transcription factors in congenital heart defects: A Commentary on a novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect

22q11 Deletion Syndrome: A Role for Tbx1 in Pharynx and Cardiovascular Development

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