Cwnt-8C: a novel Wnt gene with a potential role in primitive streak formation and hindbrain organization

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1147-1160 ◽  
Author(s):  
C.R. Hume ◽  
J. Dodd
Keyword(s):  
Gene Family ◽  
Potential Role ◽  
Marginal Zone ◽  
Cell Signalling ◽  
Primitive Streak ◽  
Axis Formation ◽  
Restricted Domain ◽  
Signalling Molecules ◽  
Wnt Proteins ◽  
Chick Embryogenesis

To begin to examine the possibility that Wnt proteins act as cell signalling molecules during chick embryogenesis, PCR was used to identify Wnt genes expressed in Hensen's node. We have identified a novel member of the Wnt gene family, Cwnt-8C, which is expressed prior to gastrulation in the posterior marginal zone, the primitive streak and Hensen's node. Injection of Cwnt-8C mRNA into Xenopus embryos caused axis duplication and dorsalization of mesodermal tissues. During neurulation, Cwnt-8C is expressed transiently in a restricted domain of the prospective hindbrain neurectoderm that will give rise to rhombomere 4. This domain is defined prior to the formation of rhombomere boundaries and also precedes the up-regulation and restriction of expression of Hox B1 in the same region. Thus, Cwnt-8C is potentially involved in the regulation of axis formation and hindbrain patterning.

Misexpression of chick Vg1 in the marginal zone induces primitive streak formation

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5127-5138 ◽  
Author(s):  
S.B. Shah ◽  
I. Skromne ◽  
C.R. Hume ◽  
D.S. Kessler ◽  
K.J. Lee ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Ectopic Expression ◽  
Primitive Streak ◽  
Axis Formation ◽  
Mesoderm Induction ◽  
Cell Fates ◽  
Signalling Molecules ◽  
Posterior Area ◽  
Area Pellucida

In the chick embryo, the primitive streak is the first axial structure to develop. The initiation of primitive streak formation in the posterior area pellucida is influenced by the adjacent posterior marginal zone (PMZ). We show here that chick Vg1 (cVg1), a member of the TGFbeta family of signalling molecules whose homolog in Xenopus is implicated in mesoderm induction, is expressed in the PMZ of prestreak embryos. Ectopic expression of cVg1 protein in the marginal zone chick blastoderms directs the formation of a secondary primitive streak, which subsequently develops into an ectopic embryo. We have used cell marking techniques to show that cells that contribute to the ectopic primitive streak change fate, acquiring two distinct properties of primitive streak cells, defined by gene expression and cell movements. Furthermore, naive epiblast explants exposed to cVg1 protein in vitro acquire axial mesodermal properties. Together, these results show that cVg1 can mediate ectopic axis formation in the chick by inducing new cell fates and they permit the analysis of distinct events that occur during primitive streak formation.

Interactions between Wnt and Vg1 signalling pathways initiate primitive streak formation in the chick embryo

Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 2915-2927 ◽  
Author(s):  
Isaac Skromne ◽  
Claudio D. Stern
Keyword(s):  
Chick Embryo ◽  
Marginal Zone ◽  
Primitive Streak ◽  
Embryonic Axis ◽  
Normal Embryo ◽  
Signalling Pathways ◽  
Axis Formation ◽  
Distinct Region ◽  
Wnt Pathways ◽  
Area Pellucida

The posterior marginal zone (PMZ) of the chick embryo has Nieuwkoop centre-like properties: when transplanted to another part of the marginal zone, it induces a complete embryonic axis, without making a cellular contribution to the induced structures. However, when the PMZ is removed, the embryo can initiate axis formation from another part of the remaining marginal zone. Chick Vg1 can mimic the axis-inducing ability of the PMZ, but only when misexpressed somewhere within the marginal zone. We have investigated the properties that define the marginal zone as a distinct region. We show that the competence of the marginal zone to initiate ectopic primitive streak formation in response to cVg1 is dependent on Wnt activity. First, within the Wnt family, only Wnt8C is expressed in the marginal zone, in a gradient decreasing from posterior to anterior. Second, misexpression of Wnt1 in the area pellucida enables this region to form a primitive streak in response to cVg1. Third, the Wnt antagonists Crescent and Dkk-1 block the primitive streak-inducing ability of cVg1 in the marginal zone. These findings suggest that Wnt activity defines the marginal zone and allows cVg1 to induce an axis. We also present data suggesting some additional complexity: first, the Vg1 and Wnt pathways appear to regulate the expression of downstream components of each other’s pathway; and second, misexpression of different Wnt antagonists suggests that different classes of Wnts may cooperate with each other to regulate axis formation in the normal embryo.

Caveolin-1, galectin-3 and lipid raft domains in cancer cell signalling

2015 ◽  
Vol 57 ◽  
pp. 189-201 ◽  
Author(s):  
Jay Shankar ◽  
Cecile Boscher ◽  
Ivan R. Nabi
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Cancer Cell ◽  
Cellular Response ◽  
Spatial Organization ◽  
Essential Feature ◽  
Cell Signalling ◽  
Coated Pits ◽  
Signalling Molecules ◽  
Raft Domains

Spatial organization of the plasma membrane is an essential feature of the cellular response to external stimuli. Receptor organization at the cell surface mediates transmission of extracellular stimuli to intracellular signalling molecules and effectors that impact various cellular processes including cell differentiation, metabolism, growth, migration and apoptosis. Membrane domains include morphologically distinct plasma membrane invaginations such as clathrin-coated pits and caveolae, but also less well-defined domains such as lipid rafts and the galectin lattice. In the present chapter, we will discuss interaction between caveolae, lipid rafts and the galectin lattice in the control of cancer cell signalling.

Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Saleh A. Almatroodi ◽  
Mansoor Ali Syed ◽  
Arshad Husain Rahmani
Keyword(s):  
Clinical Trials ◽  
Cancer Cells ◽  
Active Compound ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Cell Signalling ◽  
Chemopreventive Agents ◽  
Signalling Molecules ◽  
Cancer Management ◽  
Induced Apoptosis

Background:: Curcumin, an active compound of turmeric spice is one of the most-studies natural compounds and have been widely recognized as chemopreventive agents. Several molecular mechanisms have been proven, curcumin and its analogs play a role in cancer prevention through modulating various cell signaling pathways as well as inhibition of carcinogenesis process. Objective:: To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents. Methods:: A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed central and Google scholar for the implication of curcumin in cancer management along with special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com and www.freshpatents.com. Result:: Recent studies based on cancer cells have proven that curcumin have potential effects against cancer cells, prevent the growth of cancer and act as cancer therapeutic agents. Besides, curcumin exerted anticancer effects through inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells. Conclusion:: Accumulating evidences suggest that curcumin has potentiality to inhibit cancer growth, induced apoptosis and modulate various cell signalling pathways molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy and safe dose in the management of various cancers.

Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells

2009 ◽  
Vol 417 (3) ◽  
pp. 673-683 ◽  
Author(s):  
Munetoyo Toda ◽  
Risa Hisano ◽  
Hajime Yurugi ◽  
Kaoru Akita ◽  
Kouji Maruyama ◽  
...  
Keyword(s):  
Sialic Acid ◽  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Cell Signalling ◽  
Negative Regulator ◽  
Mammary Adenocarcinoma ◽  
Marginal Zone B Cells ◽  
Tumour Bearing

CD22 [Siglec-2 (sialic acid-binding, immunoglobulin-like lectin-2)], a negative regulator of B-cell signalling, binds to α2,6- sialic acid-linked glycoconjugates, including a sialyl-Tn antigen that is one of the typical tumour-associated carbohydrate antigens expressed on various mucins. Many epithelial tumours secrete mucins into tissues and/or the bloodstream. Mouse mammary adenocarcinoma cells, TA3-Ha, produce a mucin named epiglycanin, but a subline of them, TA3-St, does not. Epiglycanin binds to CD22 and inhibits B-cell signalling in vitro. The in vivo effect of mucins in the tumour-bearing state was investigated using these cell lines. It should be noted that splenic MZ (marginal zone) B-cells were dramatically reduced in the mice bearing TA3-Ha cells but not in those bearing TA3-St cells, this being consistent with the finding that the thymus-independent response was reduced in these mice. When the mucins were administered to normal mice, a portion of them was detected in the splenic MZ associated with the MZ B-cells. Furthermore, administration of mucins to normal mice clearly reduced the splenic MZ B-cells, similar to tumour-bearing mice. These results indicate that mucins in the bloodstream interacted with CD22, which led to impairment of the splenic MZ B-cells in the tumour-bearing state.

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.

The posterior section of the chick's area pellucida and its involvement in hypoblast and primitive streak formation

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 819-830 ◽  
Author(s):  
H. Eyal-Giladi ◽  
A. Debby ◽  
N. Harel
Keyword(s):  
Distribution Pattern ◽  
Marginal Zone ◽  
Primitive Streak ◽  
Fluorescent Dye ◽  
Narrow Strip ◽  
Posterior Section ◽  
Area Pellucida

Posterior marginal zone sections with or without Koller's sickle were cut out of stage X, XI and XII E.G&K blastoderms, labelled with the fluorescent dye rhodamine-dextran-lysine (RDL) and returned to their original location. In control experiments, a similar lateral section of the marginal zone was identically treated. Different blastoderms were incubated at 37°C for different periods and were fixed after reaching stages from XII E.G&K to 4 H&H. The conclusions drawn from the analysis of the distribution pattern of the labelled cells in the serially sectioned blastoderms concern the cellular contributions to both the forming hypoblast and the forming primitive streak. Koller's sickle and the marginal zone behind it were found to contribute all the centrally located cells of the growing hypoblast. The lengthening pregastrulation PS (until stage 3+ H&H) was found to be entirely composed of epiblastic cells that at stage X were located in a narrow strip anterior to Koller's sickle. A model is proposed to integrate the results spatially and temporally.

scholarly journals Avian marginal zone cells function as primitive streak inducers only after their migration into the hypoblast

Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2501-2509 ◽  
Author(s):  
H. Eyal-Giladi ◽  
T. Lotan ◽  
T. Levin ◽  
O. Avner ◽  
J. Hochman
Keyword(s):  
Incubation Medium ◽  
Marginal Zone ◽  
Electrophoretic Pattern ◽  
Primitive Streak ◽  
Electrophoretic Analysis ◽  
Avian Embryo ◽  
Central Disc ◽  
Induction Process ◽  
Marginal Zones

Hypoblast cells of posterior marginal zone origin have been shown previously to be the inducers of primitive streak in the avian embryo. Here we checked: (1) whether the above cells acquire their inductivity while still whithin the marginal zone; (2) can inductivity be found in supernatants of defined blastodermic regions; (3) can differences in the electrophoretic pattern be shown between inducing and non-inducing tissue fragments and their conditioned media, which might give a clue as to what the inductive substance is. The following observations were made: 1. (a) Stage X chick posterior marginal zone cells prior to their migration into the hypoblast do not induce a primitive streak, when applied to a stage XIII competent epiblast central disc. (b) A posterior marginal zone fragment, when applied to an epiblast central disc, even after being preincubated for up to 9 hours in vitro, is still non-inductive. (c) Mechanically fragmented stage X posterior marginal zones when applied as a layer to epiblast central discs are non-inductive. (d) Hypoblastic tissue in strip form induces a primitive streak. 2. Competent stage XIII epiblast central discs (chick) were incubated for 2 hours in supernatants of stage XIII epiblasts or hypoblasts. Whereas no inductive effect was exerted by the epiblast supernatant, primitive streaks developed in about 50% of the epiblast central discs incubated in the hypoblast supernatant. 3. Electrophoretic analysis (quails) reveals a protein of 28x10-3 Mr that is enriched in both hypoblastic tissue and its incubation medium and not in the epiblast + marginal zone + area opaca and their incubation medium. These findings suggest a possible correlation between this protein and the induction process.

scholarly journals Molecular mechanism of symmetry breaking in a 3D model of a human epiblast

2018 ◽  
Author(s):  
Mijo Simunovic ◽  
Jakob J. Metzger ◽  
Fred Etoc ◽  
Anna Yoney ◽  
Albert Ruzo ◽  
...  
Keyword(s):  
Symmetry Breaking ◽  
Axial Symmetry ◽  
3D Model ◽  
Epithelial To Mesenchymal Transition ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Molecular Evidence ◽  
Axis Formation ◽  
Mesenchymal Transition

ABSTRACTBreaking the anterior-posterior (AP) symmetry in mammals takes place at gastrulation. Much of the signaling network underlying this process has been elucidated in the mouse, however there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro 3D model of a human epiblast whose size, cell polarity, and gene expression are similar to a 10-day human epiblast. A defined dose of bone mor-phogenetic protein 4 (BMP4) spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial to mesenchymal transition. By gene knockouts and live-cell imaging we show that, downstream of BMP4, WNT3 and its inhibitor DKK1 play key roles in this process. Our work demonstrates that a model human epiblast can break axial symmetry despite no asymmetry in the initial signal and in the absence of extraembryonic tissues or maternal cues. Our 3D model opens routes to capturing molecular events underlying axial symmetry breaking phenomena, which have largely been unexplored in model human systems.

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