scholarly journals How Dickkopf molecules and Wnt/beta-catenin interplay to self-organise the Hydra body axis

2021 ◽  
Author(s):  
Moritz Mercker ◽  
Alexey Kazarnikov ◽  
Anja Tursch ◽  
Suat Özbek ◽  
Thomas W Holstein ◽  
...  
Keyword(s):  
Pattern Formation ◽  
Numerical Study ◽  
Expression Patterns ◽  
Stem Cell Differentiation ◽  
Wnt Signalling ◽  
The Body ◽  
Body Axis ◽  
Beta Catenin ◽  
Mutual Inhibition ◽  
Activator Inhibitor

The antagonising interplay between canonical Wnt signalling and Dickkopf (Dkk) molecules has been identified in various processes involved in tissue organisation, such as stem cell differentiation and body-axis formation. Disruption of the interplay between these molecules is related to several diseases in humans. However, the detailed molecular mechanisms of the β-catenin/Wnt-Dkk interplay leading to robust formation of the body axis remain elusive. Although the β-catenin/Wnt signalling system has been shown in the pre-bilaterian model organism Hydra to interact with two ancestral Dkks (HyDkk1/2/4-A and -C) to self-organise and regenerate the body axis, the observed Dkk expression patterns do not match any current pattern-formation theory, such as the famous activator-inhibitor model. To explore the function of Dkk in Hydra patterning process, we propose a new mathematical model which accounts for the two Dkks in interplay with HyWnt3/β-catenin. Using a systematic numerical study, we demonstrate that the chosen set of interactions is sufficient to explain it de novo body-axis gradient formation in Hydra. The presented mutual inhibition model goes beyond the classical activator-inhibitor model and shows that a molecular mechanism based on mutual inhibition may replace the local activation/long-range inhibition loop. The new model is validated using a range of perturbation experiments. It resolves several contradictions between previous models and experimental data, and provides an explanation for the interplay between injury response and pattern formation.

scholarly journals A Wnt-specific astacin proteinase controls head formation in Hydra

2020 ◽  
Author(s):  
Berenice Ziegler ◽  
Irene Yiallouros ◽  
Benjamin Trageser ◽  
Sumit Kumar ◽  
Moritz Mercker ◽  
...  
Keyword(s):  
The Body ◽  
Regulatory Function ◽  
Beta Catenin ◽  
Processing Factor ◽  
Primary Body ◽  
Head Formation ◽  
Signaling Center ◽  
Sirna Knockdown ◽  
Body Column ◽  
Activator Inhibitor

AbstractThe 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 the identification of an astacin family proteinase as a Wnt processing factor. 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 levels as in transgenic actin::HyWnt3 and HyDkk1/2/4 siRNA treated animals. HyWnt3-induced double axes in Xenopus embryos could be rescued by co-injection 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.Our data suggest a negative regulatory function of Wnt processing astacin proteinases in the global patterning of the oral-aboral axis in Hydra.

scholarly journals Induction of a secondary body axis in Xenopus by antibodies to beta-catenin.

1993 ◽  
Vol 123 (2) ◽  
pp. 477-484 ◽  
Author(s):  
P D McCrea ◽  
W M Brieher ◽  
B M Gumbiner
Keyword(s):  
Cell Adhesion ◽  
The Body ◽  
Body Axis ◽  
Beta Catenin ◽  
Gene Products ◽  
Embryonic Patterning ◽  
Xenopus Embryos ◽  
Segment Polarity ◽  
Segment Polarity Gene ◽  
Polarity Gene

We have obtained evidence that a known intracellular component of the cadherin cell-cell adhesion machinery, beta-catenin, contributes to the development of the body axis in the frog Xenopus laevis. Vertebrate beta-catenin is homologous to the Drosophila segment polarity gene product armadillo, and to vertebrate plakoglobin (McCrea, P. D., C. W. Turck, and B. Gumbiner. 1991. Science (Wash. DC). 254: 1359-1361.). Beta-Catenin was found present in all Xenopus embryonic stages examined, and associated with C-cadherin, the major cadherin present in early Xenopus embryos. To test beta-catenin's function, affinity purified Fab fragments were injected into ventral blastomeres of developing four-cell Xenopus embryos. A dramatic phenotype, the duplication of the dorsoanterior embryonic axis, was observed. Furthermore, Fab injections were capable of rescuing dorsal features in UV-ventralized embryos. Similar phenotypes have been observed in misexpression studies of the Wnt and other gene products, suggesting that beta-catenin participates in a signaling pathway which specifies embryonic patterning.

scholarly journals The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Berenice Ziegler ◽  
Irene Yiallouros ◽  
Benjamin Trageser ◽  
Sumit Kumar ◽  
Moritz Mercker ◽  
...  
Keyword(s):  
The Body ◽  
Regulatory Function ◽  
Beta Catenin ◽  
Processing Factor ◽  
Primary Body ◽  
Signaling Center ◽  
Sirna Knockdown ◽  
Body Column ◽  
Activator Inhibitor ◽  
Ligand Activity

Abstract Background 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. Results 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. Conclusions 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.

scholarly journals A daf-7-related TGF-β ligand (Hc-tgh-2) shows important regulations on the development of Haemonchus contortus

2020 ◽  
Author(s):  
Li He ◽  
Hui Liu ◽  
Biying Zhang ◽  
Fangfang Li ◽  
Wenda Di ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Transforming Growth Factor ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Stem Cell Differentiation ◽  
The Body ◽  
Type I ◽  
Free Living ◽  
Developmental Transition ◽  
Third Stage

Abstract Background In most multicellular organisms, transforming growth factor-β (TGF-β) signalling pathway is involved in regulating the growth and stem cell differentiation. Previous studies have demonstrated the importance of three key molecules in this pathway in the parasitic nematode Haemonchus contortus , including one TGF-β type I receptor ( Hc-tgfbr1 ), one TGF-β type II receptor ( Hc-tgfbr2 ), and one co-Smad ( Hc-daf-3 ), which regulated the developmental transition from the free-living to the parasitic stages of this parasite. However, almost nothing is known about the function of the TGF-β ligand ( Hc-tgh-2 ) of H. contortus . Methods Here, the temporal transcription profiles of Hc-tgh-2 at eight different developmental stages and spacial expression patterns of Hc- TGH-2 in adult female and male worms of H. contortus have been examined by real-time PCR and immunohistochemistry, respectively. In addition, RNA interference (RNAi) by feeding was employed to assess the importance of Hc-tgh-2 in the development from exsheathed third-stage larvae (xL3s) to fourth-stage larvae (L4s) in H. contortus . Results Hc-tgh-2 was continuously transcribed in all eight developmental stages of H. contortus studied with the highest level in the infective third-stage larvae (iL3) and Hc -TGH-2 was located in the muscle of the body wall, intestine, ovary of adult females and testes of adult males. Silencing Hc-tgh-2 by the specific double-stranded RNA (dsRNA), decreased the transcript level of Hc-tgh-2 and resulted in fewer xL3s developing to L4s in vitro. Conclusions These results suggested that the TGF-β ligand, Hc -TGH-2, could play important roles in the developmental transition from the free-living (L3s) to the parasitic stage (L4s). Furthermore, it may also take part in the processes such as digestion, absorption, host immune response and reproductive development in H. contortus adults.

scholarly journals A daf-7-related TGF-β ligand (Hc-tgh-2) shows important regulations on the development of Haemonchus contortus

2020 ◽  
Author(s):  
Li He ◽  
Hui Liu ◽  
Biying Zhang ◽  
Fangfang Li ◽  
Wenda Di ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Transforming Growth Factor ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Stem Cell Differentiation ◽  
The Body ◽  
Type I ◽  
Free Living ◽  
Developmental Transition ◽  
Third Stage

Abstract Background In most multicellular organisms, transforming growth factor-β (TGF-β) signalling pathway is involved in regulating the growth and stem cell differentiation. Previous studies have demonstrated the importance of three key molecules in this pathway in the parasitic nematode Haemonchus contortus , including one TGF-β type I receptor ( Hc-tgfbr1 ), one TGF-β type II receptor ( Hc-tgfbr2 ), and one co-Smad ( Hc-daf-3 ), which regulated the developmental transition from the free-living to the parasitic stages of this parasite. However, almost nothing is known about the function of the TGF-β ligand ( Hc-tgh-2 ) of H. contortus . Methods Here, the temporal transcription profiles of Hc-tgh-2 at eight different developmental stages and spacial expression patterns of Hc- TGH-2 in adult female and male worms of H. contortus have been examined by real-time PCR and immunohistochemistry, respectively. In addition, RNA interference (RNAi) by soaking was employed to assess the importance of Hc-tgh-2 in the development from exsheathed third-stage larvae (xL3s) to fourth-stage larvae (L4s) in H. contortus . Results Hc-tgh-2 was continuously transcribed in all eight developmental stages of H. contortus studied with the highest level in the infective third-stage larvae (iL3) and Hc -TGH-2 was located in the muscle of the body wall, intestine, ovary of adult females and testes of adult males. Silencing Hc-tgh-2 by the specific double-stranded RNA (dsRNA), decreased the transcript level of Hc-tgh-2 and resulted in fewer xL3s developing to L4s in vitro. Conclusions These results suggested that the TGF-β ligand, Hc -TGH-2, could play important roles in the developmental transition from the free-living (L3s) to the parasitic stage (L4s). Furthermore, it may also take part in the processes such as digestion, absorption, host immune response and reproductive development in H. contortus adults.

Expression of Cnox-2, a HOM/HOX homeobox gene in hydra, is correlated with axial pattern formation

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 657-667 ◽  
Author(s):  
M.A. Shenk ◽  
H.R. Bode ◽  
R.E. Steele
Keyword(s):  
Pattern Formation ◽  
Epithelial Cells ◽  
Homeobox Gene ◽  
Specific Pattern ◽  
The Body ◽  
Body Axis ◽  
Hydra Vulgaris ◽  
Coordinate Reduction ◽  
High Level ◽  
Body Column

Cnox-2 is a HOM/HOX homeobox gene that we have identified in the simple metazoan Hydra vulgaris (Cnidaria: Hydrozoa). Cnox-2 is most closely related to anterior members of the Antennapedia gene complex from Drosophila, with the greatest similarity to Deformed. The Cnox-2 protein is expressed in the epithelial cells of adult hydra polyps in a region-specific pattern along the body axis, at a low level in the head and at a high level in the body column and the foot. The expression pattern of Cnox-2 is consistent with a role in axial pattern formation. Alteration of hydra axial patterning by treatment with diacylglycerol (DAG) results in an increase of head activation down the body column and in a coordinate reduction of Cnox-2 expression in epithelial cells in ‘head-like’ regions. These results suggest that Cnox-2 expression is negatively regulated by a signaling pathway acting through protein kinase C (PKC), and that the varying levels of expression of Cnox-2 along the body axis have the potential to result in differential gene expression which is important for hydra pattern formation.

scholarly journals Discovery of four Noggin genes in lampreys suggests two rounds of ancient genome duplication

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Galina V. Ermakova ◽  
Alexander V. Kucheryavyy ◽  
Andrey G. Zaraisky ◽  
Andrey V. Bayramov
Keyword(s):  
Functional Properties ◽  
Genome Duplication ◽  
Expression Patterns ◽  
Wnt Signalling ◽  
Beta Catenin ◽  
Secreted Protein ◽  
Spemann Organizer

AbstractThe secreted protein Noggin1 was the first discovered natural embryonic inducer produced by cells of the Spemann organizer. Thereafter, it was shown that vertebrates have a whole family of Noggin genes with different expression patterns and functional properties. For example, Noggin1 and Noggin2 inhibit the activity of BMP, Nodal/Activin and Wnt-beta-catenin signalling, while Noggin4 cannot suppress BMP but specifically modulates Wnt signalling. In this work, we described and investigated phylogeny and expression patterns of four Noggin genes in lampreys, which represent the most basally divergent group of extant vertebrates, the cyclostomes, belonging to the superclass Agnatha. Assuming that lampreys have Noggin homologues in all representatives of another superclass of vertebrates, the Gnathostomata, we propose a model for Noggin family evolution in vertebrates. This model is in agreement with the hypotheses suggesting two rounds of genome duplication in the ancestor of vertebrates before the divergence of Agnatha and Gnathostomata.

scholarly journals Bacteria- and temperature-regulated peptides modulate beta-catenin signaling in Hydra

2019 ◽  
Author(s):  
J Taubenheim ◽  
D Willoweit-Ohl ◽  
M Knop ◽  
S Franzenburg ◽  
J He ◽  
...  
Keyword(s):  
Pattern Formation ◽  
Abiotic Factors ◽  
The Body ◽  
Beta Catenin ◽  
Loss Of Function ◽  
Complex Interactions ◽  
Model Animal ◽  
Canonical Wnt ◽  
Secreted Peptides ◽  
The Impact

AbstractAnimal development has traditionally been viewed as an autonomous process directed by the host genome. But in many animals biotic and abiotic cues, like temperature and bacterial colonizers, provide signals for multiple developmental steps. Hydra offers unique features to encode these complex interactions of developmental processes with biotic and abiotic factors. Here, we used the model animal Hydra to investigate the impact of bacterial colonizers and temperature on the pattern formation process. In Hydra, formation of the head organizer involves the canonical Wnt pathway. Treatment with alsterpaullone (ALP) results in acquiring characteristics of the head organizer in the body column. Intriguingly, germ-free Hydra polyps are significantly more sensitive to ALP compared to control polyps. In addition to microbes, β-catenin dependent pattern formation is also affected by temperature. Gene expression analyses led to the identification of two small secreted peptides, named Eco1 and Eco2, being upregulated in the response to both, Curvibacter sp, the main bacterial colonizer of Hydra, and low temperatures. Loss-of function experiments revealed that Eco peptides are involved in the regulation of pattern formation and have an antagonistic function to Wnt signaling in Hydra.

scholarly journals Expression patterns of signalling molecules and transcription factors in the early rabbit embryo and their significance for modelling amniote axis formation

2021 ◽  
Author(s):  
Ruben Plöger ◽  
Christoph Viebahn
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Body Plan ◽  
The Body ◽  
Anchor Point ◽  
Axis Formation ◽  
Point Model ◽  
Signalling Molecules ◽  
Rabbit Embryo

AbstractThe anterior-posterior axis is a central element of the body plan and, during amniote gastrulation, forms through several transient domains with specific morphogenetic activities. In the chick, experimentally proven activity of signalling molecules and transcription factors lead to the concept of a ‘global positioning system’ for initial axis formation whereas in the (mammotypical) rabbit embryo, a series of morphological or molecular domains are part of a putative ‘three-anchor-point model’. Because circular expression patterns of genes involved in axis formation exist in both amniote groups prior to, and during, gastrulation and may thus be suited to reconcile these models, the expression patterns of selected genes known in the chick, namely the ones coding for the transcription factors eomes and tbx6, the signalling molecule wnt3 and the wnt inhibitor pkdcc, were analysed in the rabbit embryonic disc using in situ hybridisation and placing emphasis on their germ layer location. Peripheral wnt3 and eomes expression in all layers is found initially to be complementary to central pkdcc expression in the hypoblast during early axis formation. Pkdcc then appears — together with a posterior-anterior gradient in wnt3 and eomes domains — in the epiblast posteriorly before the emerging primitive streak is marked by pkdcc and tbx6 at its anterior and posterior extremities, respectively. Conserved circular expression patterns deduced from some of this data may point to shared mechanisms in amniote axis formation while the reshaping of localised gene expression patterns is discussed as part of the ‘three-anchor-point model’ for establishing the mammalian body plan.

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