The<i>Xenopus Brachyury</i>promoter is activated by FGF and low concentrations ofactivinandsuppressed by high concentrationsof activin and by paired-type homeodomain proteins

Latinkic, Brancko V.; Umbhauer, Muriel; Neal, Kathy A.; Lerchner, Walter; Smith, James C.; Cunliffe, Vincent T.

doi:10.1101/gad.11.23.3265

Cited by 181 publications

(166 citation statements)

References 73 publications

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“…The same relative orientation of Tcf binding sites and E boxes was found in the proximal 225 bp of the Xbra (the Xenopus T homolog), and Xbra2 (a pseudogene of Xbra) promoters (Fig. 3A,B; Artinger et al 1997;Latinkic et al 1997), which demonstrates a conservation within the regulatory region between these vertebrates, suggesting that these sequences may participate in the assembly of multiprotein enhancer complexes.…”

Section: Resultsmentioning

confidence: 74%

T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification

Yamaguchi

Takada²,

Yoshikawa³

et al. 1999

Genes & Development

479

410

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Wnt3a encodes a signal that is expressed in the primitive streak of the gastrulating mouse embryo and is required for paraxial mesoderm development. In its absence cells adopt ectopic neural fates. Embryos lacking the T-boxcontaining transcription factors, Brachyury or Tbx6, also lack paraxial mesoderm. Here we show that Brachyury is specifically down-regulated in Wnt3a mutants in cells fated to form paraxial mesoderm. Transgenic analysis of the T promoter identifies T (Brachyury) as a direct transcriptional target of the Wnt signaling pathway. Our results suggest that Wnt3a, signaling via Brachyury, modulates a balance between mesodermal and neural cell fates during gastrulation. Received September 13, 1999; revised version accepted October 13, 1999. The embryonic mesoderm of the mammalian embryo is formed by a series of inductive interactions first in the primitive streak, which gives rise to head and trunk mesoderm, and later in the tailbud, which generates the most posterior mesoderm of the tail. As development progresses, successively posterior structures are generated, leading to a posterior extension of the body axis. Previous studies have established that Wnt3a, which encodes a member of the Wnt family of secreted signaling molecules (for review, see Cadigan and Nusse 1997;Moon et al. 1997), is expressed in pluripotent ectoderm cells of the primitive streak during gastrulation (Takada et al. 1994). At early somite stages [8.0-8.5 days postcoitum (dpc)], the Wnt3a expression domain correlates with a domain of cells in the anterior primitive streak fated to give rise to paraxial mesoderm (for review, see Tam and Trainor 1994;Wilson and Beddington 1996). Moreover, the anterior and lateral limits of the Wnt3a expression domain lie between cells fated to give rise to paraxial mesoderm and cells that will give rise to neural ectoderm.A requirement for Wnt3a in the specification of trunk and tail paraxial somitic mesoderm fates has been demonstrated by mutant analyses. Wnt3a homozygous null mutant embryos lack all but the anterior-most seven to nine somites (Takada et al. 1994;Greco et al. 1996;Yoshikawa et al. 1997). As a consequence, only the most rostral cervical vertebrae are formed. Histological and molecular analyses demonstrate that ectopic neural structures form in place of posterior paraxial mesoderm (Yoshikawa et al. 1997 Mesoderm specification is thought to be regulated, at least in part, by members of the T-box gene family of DNA-binding transcription factors (Smith 1999). Two of these, T and Tbx6, are coexpressed with Wnt3a in the primitive streak during gastrulation (Takada et al. 1994;Chapman et al. 1996). Mutations in either gene lead to a loss of trunk and tail mesoderm (Chesley 1935;Chapman and Papaioannou 1998). Ectopic neural tubes form in place of paraxial mesoderm in the Tbx6 mutants, but it is not clear how similar the neural tube abnormalities noted in the T homozygotes are to the Wnt3a phenotype. Given the similarities between the Wnt3a and T-box mutant phenotypes, we have investiga...

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Section: Resultsmentioning

confidence: 74%

T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification

Yamaguchi

Takada²,

Yoshikawa³

et al. 1999

Genes & Development

479

410

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“…Specifically, goosecoid is induced only at higher activin/nodal doses and it represses Xbra expression (Artinger et al, 1997;Laurent et al, 1997;Latinkic et al, 1997;Danilov et al, 1998). Goosecoid is itself a transcriptional repressor and probably represses Xbra directly (Smith and Jaynes, 1996).…”

Section: Interpretation Of Gradients Part I: Threshold Responses Andmentioning

confidence: 99%

Morphogen gradients, positional information, and Xenopus: Interplay of theory and experiment

Green

2002

Developmental Dynamics

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The idea of morphogen gradients has long been an important one in developmental biology. Studies with amphibians and with Xenopus in particular have made significant contributions to demonstrating the existence, identity, and mechanisms of action of morphogens. Mesoderm induction and patterning by activin, nodals, bone morphogenetic proteins, and fibroblast growth factors have been analyzed thoroughly and reveal recurrent and combinatorial roles for these protein growth factor morphogens and their antagonists. The dynamics of nodal-type signaling and the intersection of VegT and ␤-catenin intracellular gradients reveal detailed steps in early long-range patterning. Interpretation of gradients requires sophisticated mechanisms for sharpening thresholds, and the activin-Xbra-Gsc system provides an example of this. The understanding of growth factor signal transduction has elucidated growth factor morphogen action and provided tools for dissecting their direct longrange action and distribution. The physical mechanisms of morphogen gradient establishment are the focus of new interest at both the experimental and theoretical level. General themes and emerging trends in morphogen gradient studies are discussed.

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“…The transcription of Xbra2, via the region 381 bp upstream of the transcription start site, is activated by FGF and low concentrations of activin but is suppressed by high concentrations of activin (Latinkić et al, 1997). This suppression is mediated by paired-type homeobox genes, goosecoid and Mix.1 (Latinkić et al, 1997;Latinkić and Smith, 1999). The Xbra expression also requires zygotic Wnt activity (Vonica and Gumbiner, 2002).…”

Section: Other Factors Controlling Ci-bra Transcriptionmentioning

confidence: 99%

“…In Xenopus embryos, Xbra and FGF constitute an autoregulatory loop (Latinkić et al, 1997;Casey et al, 1998). The transcription of Xbra2, via the region 381 bp upstream of the transcription start site, is activated by FGF and low concentrations of activin but is suppressed by high concentrations of activin (Latinkić et al, 1997).…”

Section: Other Factors Controlling Ci-bra Transcriptionmentioning

confidence: 99%

A zinc finger transcription factor, ZicL, is a direct activator ofBrachyuryin the notochord specification ofCiona intestinalis

2004

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TheXenopus Brachyurypromoter is activated by FGF and low concentrations ofactivinandsuppressed by high concentrationsof activin and by paired-type homeodomain proteins

Cited by 181 publications

References 73 publications

T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification

T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification

Morphogen gradients, positional information, and Xenopus: Interplay of theory and experiment

A zinc finger transcription factor, ZicL, is a direct activator ofBrachyuryin the notochord specification ofCiona intestinalis

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