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Genomic insights into Wnt signaling in an early diverging metazoan, the ctenophore Mnemiopsis leidyi.

Pang K, Ryan JF, NISC Comparative Sequencing ProgramMullikin JC, Baxevanis AD, Martindale MQ - Evodevo (2010)

Bottom Line: In situ hybridization of the four Wnt ligands showed that they are expressed in discrete regions associated with the aboral pole, tentacle apparati and apical organ.Furthermore, it is difficult to compare the Mnemiopsis Wnt expression patterns with those of other metazoans. mRNA expression of Wnt pathway components appears later in development than expected, and zygotic gene expression does not appear to play a role in early axis specification.Notably absent in the Mnemiopsis genome are most major secreted antagonists, which suggests that complex regulation of this secreted signaling pathway probably evolved later in animal evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawaii at Manoa, Honolulu, HI, USA. mqmartin@hawaii.edu.

ABSTRACT

Background: Intercellular signaling pathways are a fundamental component of the integrating cellular behavior required for the evolution of multicellularity. The genomes of three of the four early branching animal phyla (Cnidaria, Placozoa and Porifera) have been surveyed for key components, but not the fourth (Ctenophora). Genomic data from ctenophores could be particularly relevant, as ctenophores have been proposed to be one of the earliest branching metazoan phyla.

Results: A preliminary assembly of the lobate ctenophore Mnemiopsis leidyi genome generated using next-generation sequencing technologies were searched for components of a developmentally important signaling pathway, the Wnt/β-catenin pathway. Molecular phylogenetic analysis shows four distinct Wnt ligands (MlWnt6, MlWnt9, MlWntA and MlWntX), and most, but not all components of the receptor and intracellular signaling pathway were detected. In situ hybridization of the four Wnt ligands showed that they are expressed in discrete regions associated with the aboral pole, tentacle apparati and apical organ.

Conclusions: Ctenophores show a minimal (but not obviously simple) complement of Wnt signaling components. Furthermore, it is difficult to compare the Mnemiopsis Wnt expression patterns with those of other metazoans. mRNA expression of Wnt pathway components appears later in development than expected, and zygotic gene expression does not appear to play a role in early axis specification. Notably absent in the Mnemiopsis genome are most major secreted antagonists, which suggests that complex regulation of this secreted signaling pathway probably evolved later in animal evolution.

No MeSH data available.


Related in: MedlinePlus

Overview of Wnt/β-catenin signaling Ctenophore pathway. (A) When Wnt signaling is inactive, cytoplasmic β-catenin protein is bound by the 'destruction complex' of axin, glycogen synthase kinase 3 (GSK-3) and adenomatous polyposis coli (APC). While sequestered, GSK-3 phosphorylates β-catenin, which targets β-catenin for ubiquitination and degradation. (B) In the presence of a Wnt ligand, the pathway is activated. Wnt binds to the seven-transmembrane receptor Frizzled and its co-receptor lipoprotein receptor-related protein 5/6 (LRP5/6), which causes Dishevelled (Dsh) to be activated. Dsh inhibits GSK-3, thereby allowing β-catenin to accumulate in the cytoplasm. Eventually, β-catenin gets translocated to the nucleus, where it interacts with the transcription factor T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) to activate target genes. The diffusible antagonists (Secreted Frizzled-related (Sfrp), Dickkopf (DKK), Wnt Inhibitory Factor (WIF) and Cerberus (CER)) can modulate Wnt activity by preventing the binding of Wnt to its receptors.
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Figure 3: Overview of Wnt/β-catenin signaling Ctenophore pathway. (A) When Wnt signaling is inactive, cytoplasmic β-catenin protein is bound by the 'destruction complex' of axin, glycogen synthase kinase 3 (GSK-3) and adenomatous polyposis coli (APC). While sequestered, GSK-3 phosphorylates β-catenin, which targets β-catenin for ubiquitination and degradation. (B) In the presence of a Wnt ligand, the pathway is activated. Wnt binds to the seven-transmembrane receptor Frizzled and its co-receptor lipoprotein receptor-related protein 5/6 (LRP5/6), which causes Dishevelled (Dsh) to be activated. Dsh inhibits GSK-3, thereby allowing β-catenin to accumulate in the cytoplasm. Eventually, β-catenin gets translocated to the nucleus, where it interacts with the transcription factor T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) to activate target genes. The diffusible antagonists (Secreted Frizzled-related (Sfrp), Dickkopf (DKK), Wnt Inhibitory Factor (WIF) and Cerberus (CER)) can modulate Wnt activity by preventing the binding of Wnt to its receptors.

Mentions: In this study we examined the Wnt/β-catenin signaling pathway in the ctenophore Mnemiopsis leidyi (Figure 3). In this pathway, the absence of a Wnt ligand results in the shunting of cytoplasmic β-catenin into a 'destruction complex' of axin, adenomatous polyposis coli (APC) and glycogen synthase kinase 3 (GSK-3) [32]. GSK-3 phosphorylates specific residues in the amino terminus of β-catenin, thereby targeting β-catenin for degradation via ubiquitination. T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) interacts with the repressor Groucho to suppress specific target genes. When the Wnt ligand is present, it activates the signaling cascade by first binding to the seven-transmembrane receptor Frizzled (Fzd). Along with a co-receptor, lipoprotein receptor-related protein 5/6 (LRP5/6), Wnt binding results in the phosphorylation of Dishevelled (Dsh), thereby activating it. Dsh inhibits GSK-3 activity, which allows active, non-phosphorylated β-catenin to accumulate in the cytoplasm. Increasing levels of cytoplasmic β-catenin promotes translocation to the nucleus, where it interacts with TCF/LEF (and other cofactors) to enhance transcription of target genes. Recent work in a number of cnidarian species has shown that the Wnt pathway is evolutionarily highly conserved and plays important roles in axis and cell fate specification [33-40]. Work in the sponge Amphimedon has shown polar localization of a Wnt ligand, suggesting a role in axial specification [41]. In another species of sponge, Oscarella lobularis, Wnt/β-catenin signaling has been implicated in adult epithelial patterning and ostia formation [42]. Some components of this pathway are known to be present in Trichoplax [14,31], but their expression patterns and function are not yet known.


Genomic insights into Wnt signaling in an early diverging metazoan, the ctenophore Mnemiopsis leidyi.

Pang K, Ryan JF, NISC Comparative Sequencing ProgramMullikin JC, Baxevanis AD, Martindale MQ - Evodevo (2010)

Overview of Wnt/β-catenin signaling Ctenophore pathway. (A) When Wnt signaling is inactive, cytoplasmic β-catenin protein is bound by the 'destruction complex' of axin, glycogen synthase kinase 3 (GSK-3) and adenomatous polyposis coli (APC). While sequestered, GSK-3 phosphorylates β-catenin, which targets β-catenin for ubiquitination and degradation. (B) In the presence of a Wnt ligand, the pathway is activated. Wnt binds to the seven-transmembrane receptor Frizzled and its co-receptor lipoprotein receptor-related protein 5/6 (LRP5/6), which causes Dishevelled (Dsh) to be activated. Dsh inhibits GSK-3, thereby allowing β-catenin to accumulate in the cytoplasm. Eventually, β-catenin gets translocated to the nucleus, where it interacts with the transcription factor T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) to activate target genes. The diffusible antagonists (Secreted Frizzled-related (Sfrp), Dickkopf (DKK), Wnt Inhibitory Factor (WIF) and Cerberus (CER)) can modulate Wnt activity by preventing the binding of Wnt to its receptors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2959043&req=5

Figure 3: Overview of Wnt/β-catenin signaling Ctenophore pathway. (A) When Wnt signaling is inactive, cytoplasmic β-catenin protein is bound by the 'destruction complex' of axin, glycogen synthase kinase 3 (GSK-3) and adenomatous polyposis coli (APC). While sequestered, GSK-3 phosphorylates β-catenin, which targets β-catenin for ubiquitination and degradation. (B) In the presence of a Wnt ligand, the pathway is activated. Wnt binds to the seven-transmembrane receptor Frizzled and its co-receptor lipoprotein receptor-related protein 5/6 (LRP5/6), which causes Dishevelled (Dsh) to be activated. Dsh inhibits GSK-3, thereby allowing β-catenin to accumulate in the cytoplasm. Eventually, β-catenin gets translocated to the nucleus, where it interacts with the transcription factor T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) to activate target genes. The diffusible antagonists (Secreted Frizzled-related (Sfrp), Dickkopf (DKK), Wnt Inhibitory Factor (WIF) and Cerberus (CER)) can modulate Wnt activity by preventing the binding of Wnt to its receptors.
Mentions: In this study we examined the Wnt/β-catenin signaling pathway in the ctenophore Mnemiopsis leidyi (Figure 3). In this pathway, the absence of a Wnt ligand results in the shunting of cytoplasmic β-catenin into a 'destruction complex' of axin, adenomatous polyposis coli (APC) and glycogen synthase kinase 3 (GSK-3) [32]. GSK-3 phosphorylates specific residues in the amino terminus of β-catenin, thereby targeting β-catenin for degradation via ubiquitination. T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) interacts with the repressor Groucho to suppress specific target genes. When the Wnt ligand is present, it activates the signaling cascade by first binding to the seven-transmembrane receptor Frizzled (Fzd). Along with a co-receptor, lipoprotein receptor-related protein 5/6 (LRP5/6), Wnt binding results in the phosphorylation of Dishevelled (Dsh), thereby activating it. Dsh inhibits GSK-3 activity, which allows active, non-phosphorylated β-catenin to accumulate in the cytoplasm. Increasing levels of cytoplasmic β-catenin promotes translocation to the nucleus, where it interacts with TCF/LEF (and other cofactors) to enhance transcription of target genes. Recent work in a number of cnidarian species has shown that the Wnt pathway is evolutionarily highly conserved and plays important roles in axis and cell fate specification [33-40]. Work in the sponge Amphimedon has shown polar localization of a Wnt ligand, suggesting a role in axial specification [41]. In another species of sponge, Oscarella lobularis, Wnt/β-catenin signaling has been implicated in adult epithelial patterning and ostia formation [42]. Some components of this pathway are known to be present in Trichoplax [14,31], but their expression patterns and function are not yet known.

Bottom Line: In situ hybridization of the four Wnt ligands showed that they are expressed in discrete regions associated with the aboral pole, tentacle apparati and apical organ.Furthermore, it is difficult to compare the Mnemiopsis Wnt expression patterns with those of other metazoans. mRNA expression of Wnt pathway components appears later in development than expected, and zygotic gene expression does not appear to play a role in early axis specification.Notably absent in the Mnemiopsis genome are most major secreted antagonists, which suggests that complex regulation of this secreted signaling pathway probably evolved later in animal evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawaii at Manoa, Honolulu, HI, USA. mqmartin@hawaii.edu.

ABSTRACT

Background: Intercellular signaling pathways are a fundamental component of the integrating cellular behavior required for the evolution of multicellularity. The genomes of three of the four early branching animal phyla (Cnidaria, Placozoa and Porifera) have been surveyed for key components, but not the fourth (Ctenophora). Genomic data from ctenophores could be particularly relevant, as ctenophores have been proposed to be one of the earliest branching metazoan phyla.

Results: A preliminary assembly of the lobate ctenophore Mnemiopsis leidyi genome generated using next-generation sequencing technologies were searched for components of a developmentally important signaling pathway, the Wnt/β-catenin pathway. Molecular phylogenetic analysis shows four distinct Wnt ligands (MlWnt6, MlWnt9, MlWntA and MlWntX), and most, but not all components of the receptor and intracellular signaling pathway were detected. In situ hybridization of the four Wnt ligands showed that they are expressed in discrete regions associated with the aboral pole, tentacle apparati and apical organ.

Conclusions: Ctenophores show a minimal (but not obviously simple) complement of Wnt signaling components. Furthermore, it is difficult to compare the Mnemiopsis Wnt expression patterns with those of other metazoans. mRNA expression of Wnt pathway components appears later in development than expected, and zygotic gene expression does not appear to play a role in early axis specification. Notably absent in the Mnemiopsis genome are most major secreted antagonists, which suggests that complex regulation of this secreted signaling pathway probably evolved later in animal evolution.

No MeSH data available.


Related in: MedlinePlus