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 ◽  
...  

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.

2020 ◽  
Author(s):  
Berenice Ziegler ◽  
Irene Yiallouros ◽  
Benjamin Trageser ◽  
Sumit Kumar ◽  
Moritz Mercker ◽  
...  

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.


2021 ◽  
Author(s):  
Moritz Mercker ◽  
Alexey Kazarnikov ◽  
Anja Tursch ◽  
Suat Özbek ◽  
Thomas W Holstein ◽  
...  

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.


2020 ◽  
Vol 20 (2) ◽  
pp. 38-40
Author(s):  
A. Levitsky ◽  
A. Lapinska ◽  
I. Selivanskaya

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.


2004 ◽  
Vol 190 (8) ◽  
Author(s):  
Hiroshi Shimizu ◽  
Osamu Koizumi ◽  
Toshitaka Fujisawa
Keyword(s):  
The Body ◽  

Development ◽  
2000 ◽  
Vol 127 (1) ◽  
pp. 129-141 ◽  
Author(s):  
L. Yan ◽  
K. Fei ◽  
J. Zhang ◽  
S. Dexter ◽  
M.P. Sarras

Several members of the newly emerging astacin metalloproteinase family have been shown to function in a variety of biological events, including cell differentiation and morphogenesis during both embryonic development and adult tissue differentiation. We have characterized a new astacin proteinase, hydra metalloproteinase 2 (HMP2) from the Cnidarian, Hydra vulgaris. HMP2 is translated from a single mRNA of 1.7 kb that contains a 1488 bp open reading frame encoding a putative protein product of 496 amino acids. The overall structure of HMP2 most closely resembles that of meprins, a subgroup of astacin metalloproteinases. The presence of a transient signal peptide and a putative prosequence indicates that HMP2 is a secreted protein that requires post-translational processing. The mature HMP2 starts with an astacin proteinase domain that contains a zinc binding motif characteristic of the astacin family. Its COOH terminus is composed of two potential protein-protein interaction domains: an “MAM” domain (named after meprins, A-5 protein and receptor protein tyrosine phosphatase mu) that is only present in meprin-like astacin proteinases; and a unique C-terminal domain (TH domain) that is also present in another hydra metalloproteinase, HMP1, in Podocoryne metalloproteinase 1 (PMP1) of jellyfish and in toxins of sea anemone. The spatial expression pattern of HMP2 was determined by both mRNA whole-mount in situ hybridization and immunofluorescence studies. Both morphological techniques indicated that HMP2 is expressed only by the cells in the endodermal layer of the body column of hydra. While the highest level of HMP2 mRNA expression was observed at the junction between the body column and the foot process, immunofluorescence studies indicated that HMP2 protein was present as far apically as the base of the tentacles. In situ analysis also indicated expression of HMP2 during regeneration of the foot process. To test whether the higher levels of HMP2 mRNA expression at the basal pole related to processes underlying foot morphogenesis, antisense studies were conducted. Using a specialized technique named localized electroporation (LEP), antisense constructs to HMP2 were locally introduced into the endodermal layer of cells at the basal pole of polyps and foot regeneration was initiated and monitored. Treatment with antisense to HMP2 inhibited foot regeneration as compared to mismatch and sense controls. These functional studies in combination with the fact that HMP2 protein was expressed not only at the junction between the body column and the foot process, but also as far apically as the base of the tentacles, suggest that this meprin-class metalloproteinase may be multifunctional in hydra.


Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1211-1223 ◽  
Author(s):  
T.P. Yamaguchi ◽  
A. Bradley ◽  
A.P. McMahon ◽  
S. Jones

Morphogenesis depends on the precise control of basic cellular processes such as cell proliferation and differentiation. Wnt5a may regulate these processes since it is expressed in a gradient at the caudal end of the growing embryo during gastrulation, and later in the distal-most aspect of several structures that extend from the body. A loss-of-function mutation of Wnt5a leads to an inability to extend the A-P axis due to a progressive reduction in the size of caudal structures. In the limbs, truncation of the proximal skeleton and absence of distal digits correlates with reduced proliferation of putative progenitor cells within the progress zone. However, expression of progress zone markers, and several genes implicated in distal outgrowth and patterning including Distalless, Hoxd and Fgf family members was not altered. Taken together with the outgrowth defects observed in the developing face, ears and genitals, our data indicates that Wnt5a regulates a pathway common to many structures whose development requires extension from the primary body axis. The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells.


2012 ◽  
Vol 47 (2) ◽  
pp. 243-248 ◽  
Author(s):  
Hifza Akhtar ◽  
Lubna Tahir ◽  
Shahid Mahmud ◽  
Shahnaz Hamid

Vitamin 'A' is essential for normal growth and its deficiency causes night blindness, affects the regulatory function of skin and reduces the    general resistance of organism to infection. This deficiency does not occur by using balanced diet or by fortification of staple food with appropriate amount of Vitamin 'A'. In Pakistan vitamin 'A' fortification is done in vegetable ghee/cooking oil. It is generally assumed that  fortified amount of vitamin 'A' is fully destroyed when the food is cooked at high temperature. The present study was focused to examine the effect of Pakistani traditional cooking style on the degree of destruction of vitamin 'A' mandatory fortified in the vegetable ghee/ cooking oils. The study indicates that there are some losses of Vitamin A of the fortified oils during cooking. However in case of deep fat frying destruction of added vitamin 'A' is more pronounced. The loss of vitamin 'A' was less than 50%,  when the food was cooked in Pakistani style in case of all the cooking oils/ vegetable ghee. In prolonged frying conditions substantial amount of vitamin 'A' (45%) remains in the oil. Any how, this retention of vitamin 'A' is sufficient to meet the body requirements when oils/ghee was fortified according to the prescribed Pakistan Pure Food Rules 1965 i.e. 33,000 IU per Kg.   DOI: http://dx.doi.org/10.3329/bjsir.v47i2.11461   Bangladesh J. Sci. Ind. Res. 47(2), 243-248, 2012  


1933 ◽  
Vol 58 (1) ◽  
pp. 17-38 ◽  
Author(s):  
George A. Harrop ◽  
Louis J. Soffer ◽  
Read Ellsworth ◽  
John H. Trescher

A characteristic alteration in the electrolyte structure of the blood plasma of the suprarenalectomized dog occurs when injections of cortical extract are stopped. This alteration progresses during the course of the suprarenal insufficiency, parallel with the hemoconcentration and the loss in weight. When injections of cortical extract are resumed, the electrolyte structure returns to its original form, the alterations paralleling the dilution of the blood and the return of the body weight to its original level. The hemoconcentration, with the resulting physiological changes which take place in the suprarenalectomized dog after the cessation of cortical extract injections, is associated with a loss of sodium and chloride, accompanied by their proper complement of body water, by way of the kidney. Since this effect is produced in the suprarenalectomized animal, well nourished and in excellent condition, solely by cessation of injections of the cortical hormone, and since the reverse process of repair of the electrolyte and water losses can be effected solely by resumption of extract injections, it follows that all of the observed phenomena are due to this cause, and to this alone. It can be concluded that one function of the cortical extract in the suprarenalectomized dog is that of participation in the regulation of the sodium and chloride metabolism, and consequently, of the balance and distribution of water. The loss of water, in the absence of the cortical hormone, is sustained partly by the blood plasma, but to a far greater extent by the interstitial body fluid. The available evidence points to the kidney as the locus of this regulatory function of the cortical hormone.


2016 ◽  
Vol 371 (1685) ◽  
pp. 20150040 ◽  
Author(s):  
Y. Wenger ◽  
W. Buzgariu ◽  
B. Galliot

Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory–motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra , we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors ( Dlx , Dlx1 , DMBX1/Manacle , Ets1 , Gli3 , KLF11 , LMX1A , ZNF436 , Shox1 ), epitheliopeptides ( Arminins , PW peptide ), neurosignalling components ( CAMK1D , DDCl2 , Inx1 ), ligand-ion channel receptors ( CHRNA1 , NaC7 ), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.


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