Disease relevance of Xbra

• HIV-1 Tat effects resulted in a general suppression of gene expression, including that of Xbra and gsc, two early genes whose expression is required for proper gastrulation [1].

High impact information on Xbra

• Expression of Xbra in response to these factors is rapid, and will occur in dispersed cells and in the presence of a protein synthesis inhibitor, indicating that this is an "immediate-early" response to mesoderm induction [2].
• As with Brachyury in the mouse, Xbra is expressed in presumptive mesodermal cells around the blastopore, and then in the notochord [2].
• At the molecular level this response shows a sharp threshold of sensitivity to the dose of Xbra RNA delivered, and we suggest that Xbra may act as a genetic switch initiating posterior mesodermal specification during embryogenesis [3].
• Strong expression of Xbra messenger RNA is found in the ring of involuting mesoderm during Xenopus gastrulation, and the expression of Xbra is an immediate-early response of animal pole blastomeres to mesoderm-inducing factors [3].
• Using explants of animal pole tissue from blastula embryos, which will differentiate into mesoderm in response to activin, we show that blocking cdk5 kinase activity down-regulates the expression of the muscle marker muscle actin in response to activin, whereas the pan-mesodermal marker Xbra is unaffected [4].

Biological context of Xbra

• Here, we describe the use of hormone-inducible versions of Xbra and Pintallavis to construct cDNA libraries enriched for targets of these transcription factors [5].
• Here, we study the functional specificities of the Xenopus T-domain proteins Xbra and VegT, which differ in their abilities to induce gene expression in prospective ectodermal tissue [6].
• We show that the inability of Xbra to induce goosecoid is imposed by an N-terminal domain that interacts with the C-terminal MH2 domain of Smad1, a component of the BMP signal transduction pathway [6].
• In addition, overexpression of eFGF after the mid-blastula transition results in the up-regulation of Xbra expression during gastrula stages and causes suppression of the head and enlargement of the proctodeum, which is the converse of the posterior reductions of the FGF dominant negative receptor phenotype [7].
• We propose that Xbra functions as a switch to keep cell migration and convergent extension as mutually exclusive behaviors during gastrulation [8].

Anatomical context of Xbra

• XLPOU91 knockdown induces high levels of Xbra expression, with blastopore closure being delayed to later neurula stages [9].
• In this report, we have followed cells expressing Xbra in the presumptive trunk and tail at the gastrula stage, and find that they fate to presumptive somite, but not to ventrolateral mesoderm of the tailbud embryo [10].
• We show that during blastula stages eFGF and Xbra are able to activate the expression of each other, suggesting that they are components of an autocatalytic regulatory loop [7].
• These results suggest that Bix1 acts downstream of both VegT and Xbra to induce formation of mesoderm and endoderm [11].
• We show here that addition of low levels of basic fibroblast growth factor (bFGF) induces the ectopic expression of the mesodermal markers Xbra, MyoD and muscle actin in vegetal explants, even though vegetal cells express low levels of the FGF receptor [12].

Associations of Xbra with chemical compounds

• However, lithium induced also the expression of brachyury (Xbra) gene at very low levels [13].
• Addition of dexamethasone, which binds to the glucocorticoid receptor and releases Xbra, causes formation of mesoderm [14].
• In animal caps induced with activin, simultaneous activation of exogenous 5-hydroxytryptamine receptors inhibits both convergent extension movements associated with dorsal mesoderm induction and the expression of goosecoid, a dorsal-specific gene, but is without effect on expression of a 149 generic mesodermal marker, Xbra [15].
• The protein synthesis inhibitor cycloheximide (CHX) inhibits the activin-dependent induction of Xbra partially, while induction of Mix [16].
• Phosphoinositide cycle stimulation during treatment of explants with basic fibroblast growth factor (bFGF) synergistically increases late-phase MAPK activity and potentiates bFGF-induced expression of Xbra, a MAPK-dependent mesodermal marker [17].

Regulatory relationships of Xbra

• A dominant-negative FGF receptor (XFD) inhibits posteriorization by Xbra in a dose-dependent manner, supporting the suggestion that eFGF or a related factor has posteriorizing influence [18].
• We have previously shown that expression of Xbra alone in animal caps is sufficient to specify ventral mesoderm which expresses Xhox3 and low levels of muscle-specific actin [19].
• In addition, Xbra appears to inhibit cell migration by inhibiting adhesion to fibronectin [8].
• Otx2 represses the expression of Xbra and Xwnt-11, and the effects of IGF on gastrulation movements can be partially rescued by antisense Otx2 morpholino oligonucleotide [20].
• Ectopic Xbra can induce Xegr-1 transcription by an indirect mechanism that appears to operate via primary activation of fibroblast growth factor secretion [21].

Other interactions of Xbra

• Role of the Xlim-1 and Xbra genes in anteroposterior patterning of neural tissue by the head and trunk organizer [18].
• GATA-1b RNA injection into AC cells neither induces expression of Xbra (a general mesoderm marker) nor affects expression of XK81 (epidermal keratin) or BMP-4 and Xvent-1 (two ventral markers) [22].
• Inhibition of FGF signaling with dominant negative receptor leads to an expansion of Xnr-2 expression and to a corresponding reduction in Xbra expression [23].
• We find that maternal VegT is required for the formation of 90% of mesodermal tissue, as measured by the expression of mesodermal markers MyoD, cardiac actin, Xbra, Xwnt8 and alphaT4 globin [24].
• These results suggest that correct expression of XFGF-20 during gastrulation is required for the formation of normal head structures in Xenopus laevis during embryogenesis and that expression of the Xbra gene mediates this phenomenon [25].

Analytical, diagnostic and therapeutic context of Xbra

• To assess the role of Xbra in mesoderm formation, we increased its domain of expression in the embryo by microinjection of Xbra transcripts into the animal pole of Xenopus embryos at the one-cell stage [3].
• Whole mount in situ hybridization for the early mesodermal marker brachyury (Xbra) revealed a dramatic reduction of Xbra expression in xmi-er1-injected embryos, while mesoderm induction assays showed that overexpression of xmi-er1 significantly reduced the percentage of explants induced by FGF-2 [26].

References