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Brachyury in Xenopus (part 2/2)

Activin induces the expression of different genes in a concentration-dependent manner. The initial response of cells to activin, whether assayed in dispersed cells or in a bead-implantation regime in intact animal caps, is to activate expression of both Xbra and goosecoid. However, differential expression of the two genes, with down-regulation of Xbra, occurs very rapidly and certainly within 3 h of the initial phase of expression. This rapid refinement of gene expression can occur in dispersed cells and thus does not require cell-cell interactions. However, refinement of gene expression does require protein synthesis but not goosecoid function. Together, these results place the burden of threshold formation not on the initial induction of different genes but on regulatory interactions between the genes once they have been activated. These observations place the burden of threshold formation not on activin receptor function nor on signal transduction pathways, but on cell-autonomous events occurring after the initial activation of Xbra and goosecoid. These interactions ensure that cells cannot express both Xbra and goosecoid at the same time: the cells that go on to express goosecoid are the ones that were exposed to high doses of activin; the ones that go on to express Xbra were exposed to lower doses. This modulation of Xbra and goosecoid expression is reminiscent of normal development, when a population of cells that expresses both Xbra and goosecoid quickly resolves into two expression domains (Papin, 2000).

The nuclear, sequence-specific DNA-binding protein Xenopus Brachyury (Xbra) causes dorsal mesodermal differentiation of animal Xenopus cap ectoderm when co-expressed with the secreted proteins noggin (a protein that binds to and inactivates BMP-4, a vertebrate homolog of decapentaplegic) and Xwnt-8 (Drosophila homolog: Wingless). None of these molecules causes dorsal mesoderm formation when expressed alone. Co-expression of Xbra mRNA with noggin mRNA in animal caps specifies the main dorsal tissues, namely muscle, notochord and neural tissue. Co-expression of Xbra with Xwnt-8, in contrast, converts animal caps to muscle masses. It has been shown 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. It is now concluded that the putative transcription factor Xbra defines a cell state in the vertebrate embryo which can respond to diffusible dorsal signals such as noggin and Xwnt-8, resulting in dorsal mesodermal differentiation. In the absence of such dorsal signals Xbra causes ventral mesodermal differentiation. This state is only partially maintained after the mid-blastula transition as it permits the dorsal response to zygotically expressed noggin but it does not allow a dorsal response to zygotically expressed Xwnt-8, which elicits only ventral mesodermal differentiation (Cunliffe, 1994).

Widespread expression of the DNA-binding protein Brachyury in Xenopus animal caps causes ectopic mesoderm formation. Two types of mesoderm are induced by different concentrations of Brachyury. Animal pole explants from embryos injected with low doses of Xbra RNA differentiate into vesicles containing mesothelial smooth muscle and mesenchyme. At higher concentrations somitic muscle is formed. The transition from smooth muscle formation to that of somitic muscle occurs over a two-fold increase in Brachyury concentration. Brachyury is required for differentiation of notochord in mouse and fish embryos, but even the highest concentrations of Brachyury do not induce this tissue in Xenopus animal caps. Co-expression of Brachyury with the secreted glycoprotein noggin does cause notochord formation, but it is difficult to understand the molecular basis of this phenomenon without knowing more about the noggin signal transduction pathway. To overcome this difficulty, mesoderm-specific transcription factors have been tested for their ability to synergize with Brachyury. Co-expression of Pintallavis (a forkhead domain protein (See Drosophila forkhead) involved in axial formation), but not goosecoid (the vertebrate homolog of Drosophila Goosecoid), with Brachyury causes formation of dorsal mesoderm, including notochord. Furthermore, the effect of Pintallavis, like that of Brachyury, is dose-dependent: a two-fold increase in Pintallavis RNA causes a transition from ventral mesoderm formation to that of muscle, and a further two-fold increase induces notochord and neural tissue. These results suggest that Pintallavis cooperates with Brachyury to pattern the mesoderm in Xenopus (O'Reilly, 1995).

The Xenopus homolog of Brachyury, Xbra, is expressed in the presumptive mesoderm of the early gastrula. Induction of Xbra in animal pole tissue by activin occurs only in a narrow window of activin concentrations: if the level of inducer is too high, or too low, the gene is not expressed. It has been thought that the suppression of Xbra by high concentrations of activin is due to the action of genes such as goosecoid and a second homeobox gene Mix.1. The effects of goosecoid and Mix.1 are likely to occur at the level of transcription, because they can also repress Xbra reporter constructs. The roles played by goosecoid and Mix.1 have been examined during normal development, first in the control of Xbra expression and then in the formation of the mesendoderm. Consistent with the model outlined above, inhibition of the function of either gene product leads to transient ectopic expression of Xbra. Such embryos later develop dorsoanterior defects and, in the case of interference with Mix.1, additional defects in heart and gut formation. The phenotypes obtained in this and other studies are broadly similar in that all display loss of head, but they differ in significant details. In particular, embryos obtained following expression of myc-tagged gsc, a powerful transcriptional activator, lack a notochord and have been described as ventralized. By contrast, notochord formation is normal -- the embryos obtained in this study are best described as posteriorized. These results show that goosecoid function is required in dorsoanterior mesendoderm and not in dorsal mesoderm. Goosecoid, a transcriptional repressor, appears to act directly on transcription of Xbra. In contrast, Mix.1, which functions as a transcriptional activator, may act on Xbra indirectly, in part through activation of goosecoid (Latinkic, 1999).

A dorsal-ventral difference in the specification of mesoderm in vivo has been discovered by examining the effect of the dominant-negative FGF receptor on a new member of the Xenopus caudal (Drosophila homolog: caudal) gene family, Xcad-3. Xcad-3 is expressed throughout the marginal zone during the gastrula stages and serves as a useful marker for events occurring within the mesoderm. Disruption of the FGF signaling pathway by the dominant-negative FGF receptor, disrupts the Xcad-3 expression pattern, eliminating expression preferentially from the dorsal regions of the embryo. The expression of the Xenopus brachyury homolog, Xbra, is more readily eliminated from the dorsal than the ventral region of the embryo by the dominant-negative FGF receptor, indicating that the observed dorsal-ventral differences are not unique to Xcad-3. These results demonstrate the importance of regional effects on FGF-mediated induction in vivo and suggest that FGF-dependent expression of mesodermal genes depends upon the localization of other factors which establish dorsal-ventral differences within the embryo (Northrop, 1994).

Recently, a model to explain the mechanism of Xenopus tail bud formation has been proposed. The NMC model proposes that three regions around the late blastopore lip are required to initiate tail formation. These are the posterior-most neural plate, fated to form tail somites (M), the neural plate (N), immediately anterior to M, and the underlying caudal notochord (C). To initiate tail formation, C must underlie (and presumably signal to) the junction of N and M, which subsequently forms the tip of the tail. During normal development, the NMC interaction leading to specification of the tail bud occurs at the end of gastrulation. Outgrowth of the tail bud commences much later, becoming clearly visible by stage 30 (Beck, 1998 and references).

Several domains of the Xenopus tail bud are defined by two phases of gene expression. The first group of genes are already expressed in the tail bud region before its determination at stage 13 and are subsequently restricted in the extending tail bud by stage 30. This group, the early genes, includes the Notch ligand X-delta-1, the lim domain homeobox factor Xlim1, the T-box factor Xbra, and the homeobox factor Xnot2 and Xcad2, a member of the caudal family. X-delta-1 is expressed specifically in the posterior wall of the neuroenteric canal but is excluded from the chordoneural hinge at stage 30, thus maintaining its earlier expression in the lateral and ventral blastopore lips. Xim1 is expressed in the notochord and dorsal blastopore lip at the end of gastrulation, and is maintained in the chordoneural hinge and posterior tip of the differentiated notochord in later stages. Xnot2 is expressed in the ventral neural tube and chordoneural hinge, but not in the posterior notochord. The posterior notochord therefore represents a novel tail bud region by stage 30, marked by Xlim but not Xnot transcripts, whereas the posterior ventral neural tube is marked by Xnot but not Xbra or Xlim1. Xbra is expressed in the chordoneural hinge and posterior wall. Xcad3 expression in the posterior neural plate is later maintained in the posterior wall and posterior dorsal neural tube. Xpo is expressed in all tissues of the tail bud with the exception of the chordoneural hinge, and is expressed in the fin and epidermis (Beck 1998).

In Xenopus embryos, expression of the Xenopus homologue of Brachyury, Xbra, can be induced in presumptive ectoderm by basic fibroblast growth factor (FGF) and activin; in the absence of functional FGF or activin signalling pathways, expression of the gene is severely reduced. Ectopic expression of Xbra in presumptive ectoderm causes mesoderm to be formed. As Brachyury and its homologues encode sequence-specific DNA-binding proteins, it is likely that each functions by directly activating downstream mesoderm-specific genes. Expression in Xenopus embryos of RNA encoding a dominant-negative FGF receptor inhibits the mesoderm-inducing activity of Xbra. Ectopic expression of Xbra activates transcription of the embryonic FGF gene, and that embryonic FGF can induce expression of Xbra. This suggests that the two genes are components of a regulatory loop. Consistent with this idea, dissociation of Xbra-expressing cells causes a dramatic and rapid reduction in levels of Xbra, but the reduction can be inhibited by addition of FGF. Thus, formation of mesoderm tissue requires an intact FGF signalling pathway downstream of Brachyury. This requirement is due to a regulatory loop, in which Brachyury activates expression of a member of the FGF family, and FGF maintains expression of Brachyury (Schulte-Merker, 1995).

The tadpole larva of an ascidian develops 40 notochord cells in the center of its tail. Most of the notochord cells originate from the A-line precursors, among which inductive interactions are required for the subsequent differentiation of notochord. The presumptive-endoderm blastomeres or presumptive-notochord blastomeres themselves are inducers of notochord formation. Notochord induction takes place during the 32-cell stage. In amphibia, mesoderm induction is thought to be mediated by several growth factors, for example, activins and basic fibroblast growth factor (bFGF). In the ascidian, Halocynthia roretzi, treatment with bFGF of presumptive-notochord blastomeres that had been isolated at the early 32-cell stage promotes the formation of notochord at a low concentration of bFGF, while activin fails to induce notochord differentiation. The effect of bFGF reaches a maximum at the end of the 32-cell stage and rapidly fades at the beginning of the subsequent cleavage, the time for full induction of notochord being at least 20 minutes. The expression of As-T, an ascidian homolog of the mouse Brachyury (T) gene, starts at the 64-cell stage and is detectable exclusively in the presumptive-notochord blastomeres. The present study shows that presumptive-notochord blastomeres, isolated at the early 32-cell stage, neither differentiates into notochord nor expresses the As-T gene. However, when the presumptive-notochord blastomeres are coisolated or recombined with inducer blastomeres, transcripts of As-T are detected. When presumptive-notochord blastomeres are treated with bFGF, the expression of the As-T gene is also detected. These results suggest that inductive interaction is required for the expression of the As-T gene and that the expression of the As-T gene is closely correlated with the determined state of the notochord-precursor cells (Nakatani, 1996).

Tenascin is a large glycoprotein which is expressed in a restricted pattern in the extracellular matrix (ECM) of vertebrate embryos. Tenascin interferes with cell-fibronectin interactions in vitro, and may play a role in the control of cell migration and differentiation during development. In Xenopus, tenascin immunoreactivity is first detected at the early tailbud stage in the ECM of the most anterior somite. Thereafter, it is distributed dorsally along neural crest cell migration pathways. Tenascin mRNA is most abundant in dorsal mesoderm at the neurula stage and in somites at the early tailbud stage, indicating that the initial accumulation of tenascin in the ECM is due to secretion from paraxial mesoderm. To understand how tenascin expression in somitic mesoderm is controlled, Xbra and the myogenic factors XMyoD and XMyf5 were expressed in blastula animal cap tissue. The tenascin gene is activated by all three transcription factors. Interestingly, expression of tenascin mRNA, and accumulation of the protein in the ECM, can occur without formation of muscle. These results suggest that tenascin regionalization in early Xenopus embryos depends on tenascin RNA expression by somitic mesoderm, where it is likely to be activated by myogenic factors (Umbhauer, 1994).

Caudalization, which is proposed to be one of two functions of the amphibian organizer, initiates posterior pathways of neural development in the dorsalized ectoderm. In the absence of caudalization, dorsalized ectoderm only expresses the most anterior (archencephalic) differentiation. In the presence of caudalization, dorsalized ectrderm develops various levels of posterior neural tissues, depending on the extent of caudalization. A series of induction experiments have shown that caudalization is mediated by convergent extension: cell motility that is based on directed cell intercalation, and is essential for the morphogenesis of posterior axial tissues. During amphibian development, convergent extension is first expressed all-over the mesoderm and, after mesoderm involution, it becomes localized to the posterior mid-dorsal mesoderm, which produces notochord. This expression pattern of specific down regulation of convergent extension is also followed by the expression of the brachyury homolog. Furthermore, mouse brachyury has been implicated in the regulation of tissue elongation on the one hand, and in the control of posterior differentiation on the other. These observations suggest that protein encoded by the brachyury homolog controls the expression of convergent extension in the mesoderm. The idea is fully corroborated by a genetic study of mouse brachyury, which demonstrates that the gene product produces elongation of the posterior embryonic axis. However, there exists evidence for the induction of posterior dorsal mesodermal tissues, if brachyury homolog protein is expressed in the ectoderm. In both cases the brachyury homolog contributes to caudalization. A number of other genes appear to be involved in caudalization. The most important of these is pintallavis, which contains a fork-head DNA binding domain. It is first expressed in the marginal zone. After mesoderm involution, it is present not only in the presumptive notochord, but also in the floor plate. This is in contrast to the brachyury homolog, whose expression is restricted to mesoderm. The morphogenetic effects of exogenous RA on anteroposterior specification during amphibian embryogenesis are reviewed. The agent inhibits archencephalic differentiation and enhances differentiation of deuterencephalic and trunk levels. Thus the effect of exogenous RA on morphogenesis of CNS is very similar to that of caudalization, which is proposed to occur through the normal action of the organizer (Yamada, 1994).

Gastrulation in the amphibian embryo is driven by cells of the mesoderm. One of the genes that confers mesodermal identity in Xenopus is Brachyury (Xbra), which is required for normal gastrulation movements and ultimately for posterior mesoderm and notochord differentiation in the development of all vertebrates. Xbra is a transcription activator, and interference with transcription activation leads to an inhibition of morphogenetic movements during gastrulation. To understand this process, a screen was carried out for downstream target genes of Brachyury. This approach results in the isolation of Xwnt11, whose expression pattern is almost identical to that of Xbra at gastrula and early neurula stages. Activation of Xwnt11 is induced in an immediate-early fashion by Xbra and its expression in vivo is abolished by a dominant-interfering form of Xbra, Xbra-EnR. Overexpression of a dominant-negative form of Xwnt11 (a C-terminally truncated form of the protein), like overexpression of Xbra-EnR, inhibits convergent extension movements. This inhibition can be rescued by Dsh, a component of the Wnt signaling pathway and also by a truncated form of Dsh that cannot signal through the canonical Wnt pathway involving GSK-3 and beta-catenin. Together, these results suggest that the regulation of morphogenetic movements by Xwnt11 occurs through a pathway similar to that involved in planar polarity signaling in Drosophila (Tada, 2000).

The morphological effects of different Dishevelled constructs reveal similarities in the signaling pathways required for convergent extension in Xenopus and the establishment of planar polarity in Drosophila. In Drosophila, mutations in dsh cause defects in the orientation of cells within epithelia of the wing, thorax and eye. For example, hairs in the wing usually point distally; the dsh1 allele causes these hairs to become oriented in a highly abnormal fashion. Genetic and biochemical studies show that the 'planar polarity' signaling required to establish correct cellular orientation does not involve components usually placed downstream of Dsh, including Shaggy (GSK-3), Armadillo (beta-catenin) and Pangolin (Tcf-3). Rather, it consists of small GTPases such as RhoA and Rac followed by the activation of JNK/SAPK-like kinases. The Dsh genes have three conserved domains. The N-terminal DIX (Dishevelled-Axin) domain is involved in protein-protein interactions and is necessary for the stabilization of beta-catenin. The PDZ domain is also involved in protein-protein interactions, and may be involved in recruiting signaling proteins into larger, membrane-associated complexes. Finally, the DEP domain (Dishevelled-EGL10-Pleckstrin) is thought to be involved in G protein signaling and membrane localization and also plays a role, perhaps independent of G proteins, in activation of JNK/SAPK-like kinases (Tada, 2000 and references therein).

In Drosophila, use of transgenic embryos expressing different domain deletions reveals that the DEP domain is essential for planar polarity signaling, whereas the DIX domain, which is essential for signaling through the canonical Wnt pathway, is not involved. Similarly, in these Xenopus experiments the DEP domain (as well as the PDZ domain) but not the DIX domain is required to restore activin-induced elongation in animal caps expressing dn-wnt11. The similarities in the signaling pathways required for morphogenetic movements in Xenopus and the establishment of planar polarity in Drosophila raises the intriguing possibility that Xwnt11 may function to control cell polarity during gastrulation in Xenopus (Tada, 2000).

Tissue specification in the early embryo requires the integration of spatial information at the promoters of developmentally important genes. Although several response elements for signaling pathways have been identified in Xenopus promoters, it is not yet understood what defines the sharp borders that restrict expression to a specific tissue. Transgenic frog embryos have been used to study the spatial and temporal regulation of the Xbra promoter. Deletion analysis and point mutations in putative transcription factor-binding sites have identified two repressor modules, which exert their main effects at different stages during gastrulation. One module is defined by a bipartite binding site for a Smad-interacting protein (SIP1 - Drosophila homolog: Zn finger homeodomain 1) of the dEF1 repressor family and acts to confine expression to the marginal zone early in gastrulation. The other module is defined by two homeodomain-binding sites and is responsible for repression in dorsal mesoderm and ectoderm at mid-gastrula stages. In addition, an upstream region of the promoter is necessary to repress expression in neural tissues later in development. Together, these results show that repression plays an important role in the restriction of Xbra expression to the mesoderm, and it is suggested that similar mechanisms may be involved in the spatial regulation of other genes in early embryonic development (Lerchner, 2000).

Have Brachyury regulatory sequences been conserved during evolution? Comparison of the Xenopus and mouse Brachyury promoters reveals a region of homology corresponding to nucleotides -225 to -198 of the Xbra promoter. The 5' end of this region contains a TCF-binding site adjacent to which is an E-box motif. A similar juxtaposition of TCF site and E-box, in the opposite orientation, is found between nucleotides -118 and -96 of Xbra, and is also present in the mouse Brachyury promoter. Interestingly, mouse embryos lacking functional Wnt3a do not express Brachyury, and mutation of the TCF sites (but not of the E-boxes) prevents activation of a reporter gene in transgenic embryos, suggesting that Brachyury is a direct target of the Wnt signaling pathway. It is possible that the TCF sites are also necessary for activation of Xbra, although, while misexpression of Wnt RNA in Xenopus animal caps can activate expression of Siamois, whose promoter also contains TCF sites, Wnt signaling has not been reported to induce Xbra. This issue requires further investigation. Elsewhere within the mouse Brachyury promoter, neither Bicoid or Antennapedia class homeodomain-binding sites nor a SIP1 site have been detected (Lerchner, 2000).

Xenopus Brachyury (Xbra) plays a key role in mesoderm formation during early development. One factor thought to be involved in the regulation of Xbra is XSIP1 (Drosophila homolog: Zn finger homeodomain 1), a zinc finger/homeodomain-like DNA-binding protein that belongs to the deltaEF1 family of transcriptional repressors. Xbra and XSIP1 are co-expressed at the onset of gastrulation, but that expression subsequently refines such that Xbra is expressed in prospective mesoderm and XSIP1 in anterior neurectoderm. This refinement of the expression patterns of the two genes is due in part to the ability of XSIP1 to repress expression of Xbra. This repression is highly specific, in the sense that XSIP1 does not repress the expression of other regionally expressed genes in the early embryo, and that other members of the family to which XSIP1 belongs, such as deltaEF1 and its Xenopus homolog ZEB, cannot regulate Xbra expression. The function of XSIP1 was studied further by making an interfering construct comprising the open reading frame of XSIP1 fused to the VP16 transactivation domain. Experiments using this chimeric protein suggest that XSIP1 is required for normal gastrulation movements to occur and for the development of the anterior neural plate (Papin, 2002).

The molecular mechanisms that govern early patterning of anterior neuroectoderm (ANE) for the prospective brain region in vertebrates are largely unknown. Screening a cDNA library of Xenopus ANE led to the isolation of a Hairy and Enhancer of split- (HES)-related transcriptional repressor gene, Xenopus HES-related 1 (XHR1). XHR1 is specifically expressed in the midbrain-hindbrain boundary (MHB) region at the tailbud stage. The localized expression of XHR1 is detected as early as the early gastrula stage in the presumptive MHB region, an area just anterior to the involuting dorsal mesoderm, demarcated by the expression of the gene Xbra. Expression of XHR1 is detected much earlier than that of other known MHB genes (XPax-2 and En-2) and also before the formation of the expression boundary between Xotx2 and Xgbx-2, suggesting that the early patterning of the presumptive MHB is independent of Xotx2 and Xgbx-2. Instead, the location of XHR1 expression appears to be determined in relation to the Xbra expression domain, since reduced or ectopic expression of Xbra alters the XHR1 expression domain according to the location of Xbra expression. In functional assays using mRNA injection, overexpression of dominant-negative forms of XHR1 in the MHB region led to marked reduction of XPax-2 and En-2 expression, and this phenotype was rescued by coexpression of wild-type XHR1. Furthermore, ectopically expressed wild-type XHR1 near the MHB region enhances En-2 expression only in the MHB region but not in the region outside the MHB. These data suggest that XHR1 is required, but not sufficient by itself, to initiate MHB marker gene expression. Based on these data, it is proposed that XHR1 demarcates the prospective MHB region in the neuroectoderm in Xenopus early gastrulae (Shinga, 2001).

Different cell types that occupy the midline of vertebrate embryos originate within the Spemann-Mangold or gastrula organizer. One such cell type is hypochord, which lies ventral to notochord in anamniote embryos. Hypochord precursors arise from the lateral edges of the organizer in zebrafish. During gastrulation, hypochord precursors are closely associated with the Brachyury homolog no tail-expressing midline precursors and paraxial mesoderm; these mesoderm cells also express deltaC and deltaD. Loss-of-function experiments have revealed that deltaC and deltaD are required for her4 expression in presumptive hypochord precursors and for hypochord development. Conversely, ectopic, unregulated Notch activity blocks no tail expression and promotes her4 expression. It is proposed that Delta signaling from paraxial mesoderm diversifies midline cell fate by inducing a subset of neighboring midline precursors to develop as hypochord, rather than as notochord (Latimer, 2002).

How might Delta signals induce hypochord development? One key might be regulation of ntl expression. ntl mutant embryos lack notochord and rostral hypochord and have excess floor plate. It has been proposed that ntl regulates a midline precursor fate decision by promoting notochord and inhibiting floor-plate development. It is further proposed that modulation of ntl expression within midline precursors by Delta-Notch signaling is required for hypochord development. In this model, ntl promotes formation of a population of midline precursors that have the potential to develop either as notochord or hypochord. Activation of Notch in a subset of precursors by Delta ligands expressed by neighboring paraxial mesoderm cells induces her4 and represses ntl expression. Consistent with this, constitutive Notch activity can cell-autonomously drive ectopic her4 expression. In the absence of Notch activity, her4 expression is not induced, and excess midline cells express ntl. Thus, Notch activity diverts midline precursors from notochord to hypochord fate (Latimer, 2002).

During Xenopus gastrulation, the dorsal mesoderm exhibits two different cell behaviors in two different regions: active cell migration of prechordal mesoderm and convergent extension of chordamesoderm. Although many genes involved in specification and differentiation of the dorsal mesoderm have been studied, the role of these genes in controlling cell behaviors is poorly understood. To understand better the link between the development and cell behaviors of the dorsal mesoderm, these behaviors were examined in dissociated cells and explants, where activin protein can induce both active cell migration and convergent extension. Xbra, a transcription factor necessary for convergent extension, actively inhibits cell migration, both in animal cap explant assays and in the endogenous dorsal mesoderm. In addition, Xbra appears to inhibit cell migration by inhibiting adhesion to fibronectin. It is proposed that Xbra functions as a switch to keep cell migration and convergent extension as mutually exclusive behaviors during gastrulation (Kwan, 2003).

Members of the T-box gene family play important and diverse roles in development and disease. Functional specificities of the Xenopus T-domain proteins Xbra and VegT, which differ in their abilities to induce gene expression in prospective ectodermal tissue, has been studied. In particular, VegT induces strong expression of goosecoid whereas Xbra cannot. These results indicate that Xbra is unable to induce goosecoid because it directly activates expression of Xom, a repressor of goosecoid that acts downstream of BMP signaling. 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. Interference with this interaction causes ectopic activation of goosecoid and anteriorization of the embryo. These findings suggest a mechanism by which individual T-domain proteins may interact with different partners to elicit a specific response (Messenger, 2005).

Table of contents

brachyenteron: Biological Overview | Regulation | Developmental Biology | Effects of Mutation | References

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