Characterization of a Smad Motif Similar to Drosophila Mad in the Mouse Msx 1 Promoter

Martı́nez, Consuelo; Binato, Renata; Gonzalez, Sayonara; Pereira, M; Robert, Benoît; Abdelhay, Eliana

doi:10.1006/bbrc.2002.6502

Cited by 25 publications

(5 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evidence cited in favor of the “activation” model include the fact that over-expression of BMPs in Xenopus can induce Msx1 expression in the presence of cyclohexamide, suggesting a direct activation of Msx1 by BMPs [ 53 ]. Also, Msx1 and Msx2 promoter elements have been identified that mediate BMP-dependent activation of reporter gene constructs [ 54 – 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is also noteworthy that while minimal Msx enhancer elements have been described to respond positively to BMP signaling and drive parts of the endogenous gene expression profiles, none of these elements drive expression in the dorsal region of the neural plate [ 54 – 56 ]. Thus, it remains to be determined whether Msx1/2 genes are activated directly by BMP signaling in the dorsal neural tube or indirectly by relieving cross-inhibition mediated by more ventrally expressed transcription factors such as Gsh, Pax6, or Dbx1,2.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Threshold-Dependent BMP-Mediated Repression: A Model for a Conserved Mechanism That Patterns the Neuroectoderm

et al. 2006

View full text Add to dashboard Cite

Subdivision of the neuroectoderm into three rows of cells along the dorsal-ventral axis by neural identity genes is a highly conserved developmental process. While neural identity genes are expressed in remarkably similar patterns in vertebrates and invertebrates, previous work suggests that these patterns may be regulated by distinct upstream genetic pathways. Here we ask whether a potential conserved source of positional information provided by the BMP signaling contributes to patterning the neuroectoderm. We have addressed this question in two ways: First, we asked whether BMPs can act as bona fide morphogens to pattern the Drosophila neuroectoderm in a dose-dependent fashion, and second, we examined whether BMPs might act in a similar fashion in patterning the vertebrate neuroectoderm. In this study, we show that graded BMP signaling participates in organizing the neural axis in Drosophila by repressing expression of neural identity genes in a threshold-dependent fashion. We also provide evidence for a similar organizing activity of BMP signaling in chick neural plate explants, which may operate by the same double negative mechanism that acts earlier during neural induction. We propose that BMPs played an ancestral role in patterning the metazoan neuroectoderm by threshold-dependent repression of neural identity genes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Threshold-Dependent BMP-Mediated Repression: A Model for a Conserved Mechanism That Patterns the Neuroectoderm

et al. 2006

View full text Add to dashboard Cite

show abstract

“…It has been established that Msx genes are a direct target of Bmp signaling in several animal models, and that Msx gene promoter elements respond to Smad proteins that are directly activated by the Bmp ligand Takahashi et al, 1997;Gonzalez et al, 1998;Alvarez-Martinez et al, 2002). In addition, at early stages of ectodermal patterning in Xenopus and zebrafish, the Msx genes and the Bmp factors are expressed in the same region, supporting the idea that the first are regulated by Bmp activity.…”

Section: Control Of Msx Gene Transcription By Bmp Signallingmentioning

confidence: 99%

Regulation of Msx genes by a Bmp gradient is essential for neural crest specification

et al. 2003

View full text Add to dashboard Cite

There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail,slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest genetic cascade. In order to study the hierarchical relationship between msx1and snail/slug we performed several rescue experiments using dominant negatives for these genes. The rescuing activity by snail and slug on neural crest development of the msx1 dominant negative, together with the inability of msx1 to rescue the dominant negatives of slug and snail strongly argue that msx1 is upstream of snail and slug in the genetic cascade that specifies the neural crest in the ectoderm. We propose a model where a gradient of Bmp activity specifies the expression of Msx genes in the neural folds, and that this expression is essential for the early specification of the neural crest.

show abstract

“…The msx1 and msx2 genes are required for the formation of neural crest cells and stimulate the expression of additional early neural crest marker genes, including snail, slug and foxd3 (Tribulo et al, 2003;Khadka et al, 2006). The msx1 gene is a direct target of the BMP signal transduction pathway (Takahashi et al, 1997;Alvarez-Martinez et al, 2002), but the transcriptional activation of msx1 is dose-dependent and requires intermediate levels of BMP signalling activity. Therefore, the territory expressing msx-1 is expanded in Xenopus and zebrafish embryos with reduced BMP signalling activity, and locally applied Noggin protein can induce ectopic msx1 expression in neighbouring tissues (Nguyen et al, 2000;Tribulo et al, 2003).…”

Section: Negative Regulation Of Tgf-β Signalling By Galntl-1mentioning

confidence: 99%

Regulation of TGF-β signalling by N-acetylgalactosaminyltransferase-like 1

et al. 2008

View full text Add to dashboard Cite

The TGF-β superfamily of secreted signalling molecules plays a pivotal role in the regulation of early embryogenesis, organogenesis and adult tissue homeostasis. Here we report the identification of Xenopus N-acetylgalactosaminyltransferase-like 1 (xGalntl-1) as a novel important regulator of TGF-β signalling. N-acetylgalactosaminyltransferases mediate the first step of mucin-type glycosylation, adding N-acetylgalactose to serine or threonine side chains. xGalntl-1 is expressed in the anterior mesoderm and neural crest territory at neurula stage, and in the anterior neural crest, notochord and the mediolateral spinal cord at tailbud stage. Inhibition of endogenous xGalntl-1 protein synthesis, using specific morpholino oligomers, interfered with the formation of anterior neural crest, anterior notochord and the spinal cord. Xenopus and mammalian Galntl-1 inhibited Activin as well as BMP signalling in the early Xenopus embryo and in human HEK 293T cells. Gain-and loss-of-function experiments showed that xGalntl-1 interferes with the activity of the common TGF-β type II receptor ActR-IIB in vivo. In addition, our biochemical data demonstrated that xGalntl-1 specifically interferes with the binding of ActR-IIB to Activin-and BMP-specific type I receptors. This inhibitory activity of xGalntl-1 was dependent on mucin-type glycosylation, as it was sensitive to the chemical inhibitor benzyl-GalNAc. These studies reveal an important role of a N-acetylgalactosaminyltransferase in the regulation of TGF-β signalling. This novel regulatory mechanism is evolutionarily conserved and, thus, might provide a new paradigm for the regulation of TGF-β signalling in vertebrates.

show abstract

Characterization of a Smad Motif Similar to Drosophila Mad in the Mouse Msx 1 Promoter

Cited by 25 publications

References 42 publications

Threshold-Dependent BMP-Mediated Repression: A Model for a Conserved Mechanism That Patterns the Neuroectoderm

Threshold-Dependent BMP-Mediated Repression: A Model for a Conserved Mechanism That Patterns the Neuroectoderm

Regulation of Msx genes by a Bmp gradient is essential for neural crest specification

Regulation of TGF-β signalling by N-acetylgalactosaminyltransferase-like 1

Contact Info

Product

Resources

About