An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra [ChIP-Seq]
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PROVIDER: PRJNA497061 | ENA |
REPOSITORIES: ENA
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Project description:Polyps of the cnidarian Hydra maintain their adult anatomy through two developmental organizers, the head organizer located apically and the foot organizer basally. The head organizer is made of two antagonistic cross-reacting components, an activator, driving apical differentiation and an inhibitor, preventing ectopic head formation. Here we characterize the head inhibitor by comparing planarian genes down-regulated when ?-catenin is silenced to Hydra genes displaying a graded apical-to-basal expression and an up-regulation during head regeneration. We identify Sp5 as a transcription factor that fulfills the head inhibitor properties: leading to a robust multiheaded phenotype when knocked-down in Hydra, acting as a transcriptional repressor of Wnt3 and positively regulated by Wnt/?-catenin signaling. Hydra and zebrafish Sp5 repress Wnt3 promoter activity while Hydra Sp5 also activates its own expression, likely via ?-catenin/TCF interaction. This work identifies Sp5 as a potent feedback loop inhibitor of Wnt/?-catenin signaling, a function conserved across eumetazoan evolution.
| S-EPMC6338789 | BioStudies
Project description:Head regeneration in Hydra requires the transformation of gastric tissue into a head organizer that produces a head activator and a head inhibitor. Here we report the decipherment of a long-standing question in developmental biology, the identification of the transcription factor Sp5 as a key head inhibitory component. We show that Sp5 has an apical to basal graded expression pattern in intact Hydra, its expression is induced upon Wnt/β-catenin signaling activation and when knocked-down triggers the formation of multiple heads and axes in homeostatic and regenerative conditions. Our data indicate that Sp5 acts in a feed-forward loop to robustly regulate its own expression and that Sp5 prevents head formation by repressing the Wnt3 promoter. This Sp5 mediated Wnt antagonism is conserved and was invented early in metazoan evolution to set up axial patterning.
2019-01-18 | GSE121316 | GEO
Project description:Head regeneration in Hydra requires the transformation of gastric tissue into a head organizer that produces a head activator and a head inhibitor. Here we report the decipherment of a long-standing question in developmental biology, the identification of the transcription factor Sp5 as a key head inhibitory component. We show that Sp5 has an apical to basal graded expression pattern in intact Hydra, its expression is induced upon Wnt/β-catenin signaling activation and when knocked-down triggers the formation of multiple heads and axes in homeostatic and regenerative conditions. Our data indicate that Sp5 acts in a feed-forward loop to robustly regulate its own expression and that Sp5 prevents head formation by repressing the Wnt3 promoter. This Sp5 mediated Wnt antagonism is conserved and was invented early in metazoan evolution to set up axial patterning. To gain insights on the evolution of the transcriptional properties of the Sp5 gene, we analyzed the capacity of the hydra Sp5 and zebrafish Sp5a paralogs to bind to cis-regulatory elements of the contitutively active human genome and to regulate the expression of the corresponding target genes. To this end, we transfected HEK293 cells with plasmids encoding for either hySp5 or zfSp5a proteins and we performed ChIPseq and RNAseq experiments to analyze their genomic occupancies and the changes in the transcriptional profiles induced upon transfection.
2019-01-18 | GSE121317 | GEO
Project description:Head regeneration in Hydra requires the transformation of gastric tissue into a head organizer that produces a head activator and a head inhibitor. Here we report the decipherment of a long-standing question in developmental biology, the identification of the transcription factor Sp5 as a key head inhibitory component. We show that Sp5 has an apical to basal graded expression pattern in intact Hydra, its expression is induced upon Wnt/β-catenin signaling activation and when knocked-down triggers the formation of multiple heads and axes in homeostatic and regenerative conditions. Our data indicate that Sp5 acts in a feed-forward loop to robustly regulate its own expression and that Sp5 prevents head formation by repressing the Wnt3 promoter. This Sp5 mediated Wnt antagonism is conserved and was invented early in metazoan evolution to set up axial patterning.
2019-03-01 | GSE110277 | GEO
Project description:An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra
| PRJNA497058 | ENA
Project description:Polarized Wnt signaling along the primary body axis is a conserved property of axial patterning in bilaterians and prebilaterians, and depends on localized sources of Wnt ligands. However, the mechanisms governing the localized Wnt expression that emerged early in evolution are poorly understood. Here we find in the cnidarian Hydra that two functionally distinct cis-regulatory elements control the head organizer-associated Hydra Wnt3 (HyWnt3). An autoregulatory element, which mediates direct inputs of Wnt/?-catenin signaling, highly activates HyWnt3 transcription in the head region. In contrast, a repressor element is necessary and sufficient to restrict the activity of the autoregulatory element, thereby allowing the organizer-specific expression. Our results reveal that a combination of autoregulation and repression is crucial for establishing a Wnt-expressing organizing center in a basal metazoan. We suggest that this transcriptional control is an evolutionarily old strategy in the formation of Wnt signaling centers and metazoan axial patterning.
2011-01-01 | S-EPMC3107325 | BioStudies
Project description:An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra [RNA-Seq]
| PRJNA497062 | ENA
Project description:Thrombospondins (TSPs) are multidomain glycoproteins with complex matricellular functions in tissue homeostasis and remodeling. We describe a novel role of TSP as a Wnt signaling target in the basal eumetazoan Hydra. Proteome analysis identified Hydra magnipapillata TSP (HmTSP) as a major component of the cnidarian mesoglea. In general, the domain organization of cnidarian TSPs is related to the pentameric TSPs of bilaterians, and in phylogenetic analyses cnidarian TSPs formed a separate clade of high sequence diversity. HmTSP expression in polyps was restricted to the hypostomal tip and tentacle bases that harbor Wnt-regulated organizer tissues. In the hypostome, HmTSP- and Wnt3-expressing cells were identical or in close vicinity to each other, and regions of ectopic tentacle formation induced by pharmacological ?-Catenin activation (Alsterpaullone) corresponded to foci of HmTSP expression. Chromatin immunoprecipitation (ChIP) confirmed binding of Hydra TCF to conserved elements in the HmTSP promotor region. Accordingly, ?-Catenin knockdown by siRNAs reduced normal HmTSP expression at the head organizer. In contrast, knockdown of HmTSP expression led to increased numbers of ectopic organizers in Alsterpaullone-treated animals, indicating a negative regulatory function. Our data suggest an unexpected role for HmTSP as a feedback inhibitor of Wnt signaling during Hydra body axis patterning and maintenance.
| S-EPMC6079037 | BioStudies
Project description:<h4>Background</h4>The Hydra head organizer acts as a signaling center that initiates and maintains the primary body axis in steady state polyps and during budding or regeneration. Wnt/beta-Catenin signaling functions as a primary cue controlling this process, but how Wnt ligand activity is locally restricted at the protein level is poorly understood. Here we report a proteomic analysis of Hydra head tissue leading to the identification of an astacin family proteinase as a Wnt processing factor.<h4>Results</h4>Hydra astacin-7 (HAS-7) is expressed from gland cells as an apical-distal gradient in the body column, peaking close beneath the tentacle zone. HAS-7 siRNA knockdown abrogates HyWnt3 proteolysis in the head tissue and induces a robust double axis phenotype, which is rescued by simultaneous HyWnt3 knockdown. Accordingly, double axes are also observed in conditions of increased Wnt activity as in transgenic actin::HyWnt3 and HyDkk1/2/4 siRNA treated animals. HyWnt3-induced double axes in Xenopus embryos could be rescued by coinjection of HAS-7 mRNA. Mathematical modelling combined with experimental promotor analysis indicate an indirect regulation of HAS-7 by beta-Catenin, expanding the classical Turing-type activator-inhibitor model.<h4>Conclusions</h4>We show the astacin family protease HAS-7 maintains a single head organizer through proteolysis of HyWnt3. Our data suggest a negative regulatory function of Wnt processing astacin proteinases in the global patterning of the oral-aboral axis in Hydra.
| S-EPMC8191133 | BioStudies
Project description:An evolutionary conserved Sp5-Wnt3 regulatory module contributes to restrict head organizer activity in Hydra
| PRJNA433362 | ENA