Functional Specificity of the Xenopus T-Domain Protein Brachyury Is Conferred by Its Ability to Interact with Smad1

Messenger, N.J.; Kabitschke, Christin; Andrews, Robert K.; Grimmer, Donna; Miguel, Ricardo Núñez; Blundell, Tom L.; Smith, James C.; Wardle, Fiona C.

doi:10.1016/j.devcel.2005.03.001

Cited by 74 publications

(76 citation statements)

References 63 publications

(4 reference statements)

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“…This difference seems to be due to the ability of Brachyury to interact with the cofactor Smad1. This interaction, which takes place through an N-terminal domain of the Brachyury protein, allows the activation of Xom, a repressor of dorsal mesendodermal genes (30,31). We therefore compared the ability of different T-box genes to activate these target genes in Xenopus overexpression assays.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Early evolution of the T-box transcription factor family

Sebé-Pedrós

Ariza-Cosano

Weirauch

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Developmental transcription factors are key players in animal multicellularity, being members of the T-box family that are among the most important. Until recently, T-box transcription factors were thought to be exclusively present in metazoans. Here, we report the presence of T-box genes in several nonmetazoan lineages, including ichthyosporeans, filastereans, and fungi. Our data confirm that Brachyury is the most ancient member of the T-box family and establish that the T-box family diversified at the onset of Metazoa. Moreover, we demonstrate functional conservation of a homolog of Brachyury of the protist Capsaspora owczarzaki in Xenopus laevis. By comparing the molecular phenotype of C. owczarzaki Brachyury with that of homologs of early branching metazoans, we define a clear difference between unicellular holozoan and metazoan Brachyury homologs, suggesting that the specificity of Brachyury emerged at the origin of Metazoa. Experimental determination of the binding preferences of the C. owczarzaki Brachyury results in a similar motif to that of metazoan Brachyury and other T-box classes. This finding suggests that functional specificity between different T-box classes is likely achieved by interaction with alternative cofactors, as opposed to differences in binding specificity.origin multicellularity | premetazoan evolution | subfunctionalization | Porifera | Holozoa T ranscriptional regulation is a central aspect of animal development. Thus, deciphering the early evolution of metazoan transcription factors is vital for achieving a better understanding of the origin of animals. The T-box family of genes is among the most important developmental transcription factors present in Metazoa. This family is characterized by an evolutionary conserved DNA-binding domain of 180-200 amino acids, known as the T-box domain (1-3). Brachyury is the founding and best-characterized member of the T-box family, with well-established roles in blastopore specification, mesoderm differentiation and, in chordates, notochord formation (4-6). It has been hypothesized that the ancestral role of Brachyury was primarily that of blastopore determination and gastrulation (5, 7).Other T-box classes include Tbx4/5, Tbx6, Tbx2/3, Eomes, and Tbx1/15/20. With only a few exceptions (8), all classes of T-box genes are widespread among bilaterian animals, with a handful being identified and studied in nonbilaterian metazoans, such as cnidarians (5, 9), ctenophores (7, 10), and sponges (11-14). T-box genes were initially thought to be specific to metazoans (13, 15), but two recent studies revealed the presence of T-box genes in nonmetazoan lineages (14, 16), including the unicellular filose amoeba Capsaspora owczarzaki, a close relative of animals, and the chytrid fungus Spizellomyces punctatus. T-box genes were not identified in any other sequenced eukaryote, suggesting that T-box genes were secondarily lost in choanoflagellates (both in unicellular and colonial species) and most fungi. Interestingly, one of the T-box genes identified in C. ow...

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Section: Resultsmentioning

confidence: 99%

“…Ref. 30 proposed that an N-terminal domain is responsible for the interaction between Brachyury and Smad1, which would restrict its function spatially. Indeed organisms whose Brachyury lack this domain, such as Drosophila Bra or ascidian Bra, are unable to behave as endogenous XBra (31).…”

Section: Resultsmentioning

confidence: 99%

Early evolution of the T-box transcription factor family

Sebé-Pedrós

Ariza-Cosano

Weirauch

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Continued elongation of the tail bud requires the action of the transcription factors Brachyury (Wacker et al, 2004b;Messenger et al, 2005) and Caudal (Pownall et al, 1996;Charite et al, 1998;Isaacs et al, 1998;Pownall et al, 1998;van den Akker et al, 2002;Chawengsaksophak et al, 2004;Copf et al, 2004;Beland and Lohnes, 2005). Misexpression of Brachyury mRNA in the frog induces only caudal structures whereas misexpression of a related T-box gene, VegT, induces head structures.…”

Section: The Tail Bud and Completion Of The Gross Patternmentioning

confidence: 99%

“…Misexpression of Brachyury mRNA in the frog induces only caudal structures whereas misexpression of a related T-box gene, VegT, induces head structures. Intriguingly this seems to be due to differential affinities of these transcription factors for the BMP effector Smad1: a C-terminal sequence in Brachyury is required for this interaction; if it is mutated, Brachyury can induce head structures (Messenger et al, 2005). This reveals the critical role of Brachyury in caudal extension, but it also provides another reminder of how difficult it is to disentangle the head-tail axis from dorsoventral patterning when misexpressing genes at early stages, since mutating the Smad1-interacting sequence in Brachyury also induces expression of the organizer (dorsal) marker goosecoid.…”

Section: The Tail Bud and Completion Of The Gross Patternmentioning

confidence: 99%

Head-tail patterning of the vertebrate embryo: one, two or many unresolved problems?

Stern

Charité²,

Deschamps³

et al. 2006

Int. J. Dev. Biol.

132

113

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When, where and how is the head-tail axis of the embryo set up during development? These are such fundamental and intensely studied questions that one might expect them to have been answered long ago. Not so; we still understand very little about the cellular or molecular mechanisms that lead to the orderly arrangement of body elements along the head-tail axis in vertebrates. In this paper, we outline some of the major outstanding problems and controversies and try to identify some reasons why it has been so difficult to resolve this important issue

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“…Of interest, Bmp signaling and T have been found to genetically cooperate in tailbud progenitor cell differentiation (O'Neill and Thorpe, 2013). T was also reported to interact with the Bmp signaling molecule Smad1 (Messenger et al, 2005). Hence, the immediate response gene T might cooperate with Bmp-Smad signaling to promote the full mesoderm progenitor transcriptional response.…”

Section: Chx) (B) Qrt-pcr For Msgn1 Andmentioning

confidence: 99%

Bmp signaling maintains a mesoderm progenitor cell state in the mouse tailbud

Sharma¹,

Shafer²,

Bareke³

et al. 2017

Journal of Cell Science

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Caudal somites are generated from a pool of progenitor cells located in the tailbud region. These progenitor cells form the presomitic mesoderm that gradually differentiates into somites under the action of the segmentation clock. The signals responsible for tailbud mesoderm progenitor pool maintenance during axial elongation are still elusive. Here, we show that Bmp signaling is sufficient to activate the entire mesoderm progenitor gene signature in primary cultures of caudal mesoderm cells. Bmp signaling acts through the key regulatory genes brachyury (T ) and Nkx1-2 and contributes to the activation of several other regulators of the mesoderm progenitor gene network. In the absence of Bmp signaling, tailbud mesoderm progenitor cells acquire aberrant gene expression signatures of the heart, blood, muscle and skeletal embryonic lineages. Treatment of embryos with the Bmp inhibitor noggin confirmed the requirement for Bmp signaling for normal T expression and the prevention of abnormal lineage marker activation. Together, these results identify Bmp signaling as a non-cell-autonomous signal necessary for mesoderm progenitor cell homeostasis.

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Functional Specificity of the Xenopus T-Domain Protein Brachyury Is Conferred by Its Ability to Interact with Smad1

Cited by 74 publications

References 63 publications

Early evolution of the T-box transcription factor family

Early evolution of the T-box transcription factor family

Head-tail patterning of the vertebrate embryo: one, two or many unresolved problems?

Bmp signaling maintains a mesoderm progenitor cell state in the mouse tailbud

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