scholarly journals Xwnt11 and the regulation of gastrulation in Xenopus

2000 ◽  
Vol 355 (1399) ◽  
pp. 923-930 ◽  
Author(s):  
J.C. Smith ◽  
Frank L. Conlon ◽  
Yasushi Saka ◽  
Masazumi Tada
Keyword(s):  
Cell Shape ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Small Gtpases ◽  
Mouse Embryos ◽  
Dominant Negative ◽  
Transduction Pathway ◽  
Transcription Activator ◽  
Canonical Wnt ◽  
Future Work

The molecular basis of gastrulation is poorly understood. In this paper we address this problem by taking advantage of the observation that the transcription activator Brachyury is essential for gastrulation movements in Xenopus and mouse embryos. We infer from this observation that amongst the target genes of Brachyury are some that are involved in the regulation of gastrulation. In the course of a screen for Brachyury targets we identified Xwnt11 . Use of a dominant-negative Xwnt11 construct confirms that signalling by this class of Wnts is essential for normal gastrulation movements, and further investigation suggests that Xwnt11 signals not through the canonical Wnt signalling pathway involving GSK-3 and β-catenin but through another route, which may require small GTPases such as Rho and Rac. Future work will concentrate on elucidating the Xwnt11 signal transduction pathway and on investigating its influence on cell shape and polarity during Xenopus gastrulation.

Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway

Development ◽  
2000 ◽  
Vol 127 (10) ◽  
pp. 2227-2238 ◽  
Author(s):  
M. Tada ◽  
J.C. Smith
Keyword(s):  
Wnt Pathway ◽  
Target Genes ◽  
Dominant Negative ◽  
Beta Catenin ◽  
Transcription Activator ◽  
Amphibian Embryo ◽  
Morphogenetic Movements ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

Gastrulation in the amphibian embryo is driven by cells of the mesoderm. One of the genes that confers mesodermal identity in Xenopus is Brachyury (Xbra), which is required for normal gastrulation movements and ultimately for posterior mesoderm and notochord differentiation in the development of all vertebrates. Xbra is a transcription activator, and interference with transcription activation leads to an inhibition of morphogenetic movements during gastrulation. To understand this process, we have screened for downstream target genes of Brachyury (Tada, M., Casey, E., Fairclough, L. and Smith, J. C. (1998) Development 125, 3997–4006). This approach has now allowed us to isolate Xwnt11, whose expression pattern is almost identical to that of Xbra at gastrula and early neurula stages. Activation of Xwnt11 is induced in an immediate-early fashion by Xbra and its expression in vivo is abolished by a dominant-interfering form of Xbra, Xbra-En(R). Overexpression of a dominant-negative form of Xwnt11, like overexpression of Xbra-En(R), inhibits convergent extension movements. This inhibition can be rescued by Dsh, a component of the Wnt signalling pathway and also by a truncated form of Dsh which cannot signal through the canonical Wnt pathway involving GSK-3 and (beta)-catenin. Together, our results suggest that the regulation of morphogenetic movements by Xwnt11 occurs through a pathway similar to that involved in planar polarity signalling in Drosophila.

Hemojuvelin Acts as a Bone Morphogenetic Protein Co-Receptor To Regulate Hepcidin Expression.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 511-511 ◽  
Author(s):  
Franklin W. Huang ◽  
Jodie L. Babitt ◽  
Diedra M. Wrighting ◽  
Tarek A. Samad ◽  
Yin Xia ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Bone Morphogenetic Protein ◽  
Signal Transduction Pathway ◽  
Bmp Signaling ◽  
Dominant Negative ◽  
Transduction Pathway ◽  
Reporter Construct ◽  
Hepcidin Expression ◽  
Morphogenetic Protein ◽  
Juvenile Hemochromatosis

Abstract Juvenile hemochromatosis is a severe iron overload disorder resulting from mutations in the hemojuvelin (HJV) gene. To understand its pathogenesis, we developed Hjv−/− mice. Similar to human patients, Hjv−/− animals accumulate excess iron in the liver, pancreas and heart early in life. Tissue macrophages are iron-depleted. Hjv−/− mice express very low levels of hepcidin mRNA and, likely as a consequence, have elevated expression of the iron transporter ferroportin in enterocytes and macrophages. These results suggested that Hjv plays a role in regulating hepcidin expression. Two known Hjv homologs, Rgma and Rgmb, have previously been shown to act as bone morphogenetic protein (BMP) co-receptors. We hypothesized that Hjv regulates hepcidin expression through a BMP signal transduction pathway. We found that Hjv binds radiolabeled BMP, supporting the contention that it is a BMP co-receptor. Transfection of HepG2 cells with Hjv cDNA activated a BMP-responsive reporter construct and augmented its response to exogenous BMP. Both an anti-BMP neutralizing antibody and the natural BMP antagonist Noggin blocked this response, as did co-expressed dominant negative BMP receptor proteins. When cells were transfected with a construct carrying an Hjv mutation known to cause human disease, BMP reporter activation was significantly reduced in the presence and absence of exogenous BMP. Treatment with BMP stimulated hepcidin production in hepatoma cells and activated a reporter construct containing a fragment of the hepcidin promoter. To extend these results, we studied tissues from Hjv−/− mice. BMP signals are transduced through phosphorylation of Smad proteins. We found that Smads 1, 5 and 8 were hypophosphorylated in Hjv−/− liver, consistent with impaired BMP signaling. BMP treatment of wild type and Hjv−/− primary hepatocytes induced hepcidin expression, but induction was blunted in cells from Hjv−/− animals. Taken together, these data suggest that the normal hepatic function of Hjv is to serve as a BMP co-receptor, modulating a signal transduction pathway that culminates in hepcidin expression. [Note - Jodie L. Babitt is the first author of this abstract, but it will be presented by Franklin W. Huang, the second author]

scholarly journals Genetic Evidence for a Protein Kinase A/Cubitus Interruptus Complex That Facilitates Processing of Cubitus Interruptus in Drosophila

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1157-1166
Author(s):  
John A Kiger ◽  
Cristin O'Shea
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Target Gene ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Cubitus Interruptus ◽  
Mutant Forms ◽  
The Relationship ◽  
Kinase A

Abstract Hedgehog (Hh) activates a signal transduction pathway regulating Cubitus interruptus (Ci). In the absence of Hh, full-length Ci (Ci-155) is bound in a complex that includes Costal2 (Cos2) and Fused (Fu). Ci-155 is phosphorylated by protein kinase A (PKA), inducing proteolysis to Ci-75, a transcriptional repressor. Hh signaling blocks proteolysis and produces an activated Ci-155 transcriptional activator. The relationship between PKA and the Ci/Cos2/Fu complex is unclear. Here we examine Hh target gene expression caused by mutant forms of PKA regulatory (PKAr) and catalytic (PKAc) subunits and by the PKAc inhibitor PKI(1-31). The mutant PKAr*, defective in binding cAMP, is shown to activate Hh target genes solely through its ability to bind and inhibit endogenous PKAc. Surprisingly, PKAcA75, a catalytically impaired mutant, also activates Hh target genes. To account for this observation, we propose that PKAc phosphorylation targeting Ci-155 for proteolysis is regulated within a complex that includes PKAc and Ci-155 and excludes PKI(1-31). This complex may permit processive phosphorylation of Ci-155 molecules, facilitating their processing to Ci-75.

scholarly journals Genetic evidence for signal transduction within the Bacillus subtilis GerA germinant receptor

2021 ◽  
Author(s):  
Jeremy D. Amon ◽  
Lior Artzi ◽  
David Z. Rudner
Keyword(s):  
Signal Transduction ◽  
Bacillus Subtilis ◽  
Signal Transduction Pathway ◽  
Dominant Negative ◽  
Transduction Pathway ◽  
Sense And Respond ◽  
Enrichment Strategy ◽  
Functional Receptor

Bacterial spores can rapidly exit dormancy through the process of germination. This process begins with the activation of nutrient receptors embedded in the spore membrane. The prototypical germinant receptor in Bacillus subtilis responds to L-alanine and is thought to be a complex of proteins encoded by the genes in the gerA operon: gerAA , gerAB , and gerAC . The GerAB subunit has recently been shown to function as the nutrient sensor, but beyond contributing to complex stability, no additional functions have been attributed to the other two subunits. Here, we investigate the role of GerAA. We resurrect a previously characterized allele of gerA (termed gerA* ) that carries a mutation in gerAA and show it constitutively activates germination even in the presence of a wild-type copy of gerA . Using an enrichment strategy to screen for suppressors of gerA* , we identified mutations in all three gerA genes that restore a functional receptor. Characterization of two distinct gerAB suppressors revealed that one ( gerAB[E105K]) reduces the GerA complex's ability to respond to L-alanine, while another ( gerAB[F259S] ) disrupts the germinant signal downstream of L-alanine recognition. These data argue against models in which GerAA is directly or indirectly involved in germinant sensing. Rather, our data suggest that GerAA is responsible for transducing the nutrient signal sensed by GerAB. While the steps downstream of gerAA have yet to be uncovered, these results validate the use of a dominant-negative genetic approach in elucidating the gerA signal transduction pathway. Importance Endospore formers are a broad group of bacteria that can enter dormancy upon starvation and exit dormancy upon sensing the return of nutrients. How dormant spores sense and respond to these nutrients is poorly understood. Here, we identify a key step in the signal transduction pathway that is activated after spores detect the amino acid L-alanine. We present a model that provides a more complete picture of this process that is critical for allowing dormant spores to germinate and resume growth.

scholarly journals An Efficient Method to Identify Conditionally Activated Transcription Factors and their Corresponding Signal Transduction Pathway Segments

2009 ◽  
Vol 3 ◽  
pp. BBI.S3485
Author(s):  
Haiyan Hu
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Efficient Method ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Protein Interaction Data ◽  
Transduction Pathway ◽  
Binding Data ◽  
Microarray Datasets

A signal transduction pathway (STP) is a cascade composed of a series of signal transferring steps, which often activate one or more transcription factors (TFs) to control the transcription of target genes. Understanding signaling pathways is important to our understanding of the molecular mechanisms of disease. Many condition-annotated pathways have been deposited in public databases. However, condition-annotated pathways are far from complete, considering the large number of possible conditions. Computational methods to assist in the identification of conditionally activated pathways are greatly needed. In this paper, we propose an efficient method to identify conditionally activated pathway segments starting from the identification of conditionally activated TFs, by incorporating protein-DNA binding data, gene expression data and protein interaction data. Applying our methods on several microarray datasets, we have discovered many significantly activated TFs and their corresponding pathway segments, which are supported by evidence in the literature.

scholarly journals Copper Response Element and Crr1-Dependent Ni2+-Responsive Promoter for Induced, Reversible Gene Expression in Chlamydomonas reinhardtii

2003 ◽  
Vol 2 (5) ◽  
pp. 995-1002 ◽  
Author(s):  
Jeanette M. Quinn ◽  
Janette Kropat ◽  
Sabeeha Merchant
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Chlamydomonas Reinhardtii ◽  
Target Genes ◽  
Response Regulator ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Nickel Ions ◽  
Cobalt Ions ◽  
Inducible Gene

ABSTRACT The Cpx1 and Cyc6 genes of Chlamydomonas reinhardtii are activated in copper-deficient cells via a signal transduction pathway that requires copper response elements (CuREs) and a copper response regulator defined by the CRR1 locus. The two genes can also be activated by provision of nickel or cobalt ions in the medium. The response to nickel ions requires at least one CuRE and also CRR1 function, suggesting that nickel interferes with a component in the nutritional copper signal transduction pathway. Nickel does not act by preventing copper uptake/utilization because (i) holoplastocyanin formation is unaffected in Ni2+-treated cells and (ii) provision of excess copper cannot reverse the Ni-dependent activation of the target genes. The CuRE is sufficient for conferring Ni-responsive expression to a reporter gene, which suggests that the system has practical application as a vehicle for inducible gene expression. The inducer can be removed either by replacing the medium or by chelating the inducer with excess EDTA, either of which treatments reverses the activation of the target genes.

scholarly journals Transcriptome and phytochemical analyses provide new insights into long non-coding RNAs and characteristic secondary metabolites of oolong tea (Camellia sinensis) in solar-withering

2019 ◽  
Author(s):  
Chen Zhu ◽  
Shuting Zhang ◽  
Haifeng Fu ◽  
Chengzhe Zhou ◽  
Lan Chen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Secondary Metabolites ◽  
Metabolic Pathway ◽  
Target Genes ◽  
Expression Profiles ◽  
Signal Transduction Pathway ◽  
Total Flavonoid ◽  
Transduction Pathway ◽  
Oolong Tea ◽  
Non Coding Rnas

Abstract Background Oolong tea, a semi-fermented tea, was deeply loved by consumers. Among tea processing, withering is the first indispensable process for improving the unique flavor. However, the roles of long non-coding RNAs (lncRNAs) and characteristic secondary metabolites in withering of oolong tea remain unknown. Results Using phytochemical analyses, the total flavonoid, total catechins, EGC, CG, GCG, ECG, and EGCG were all present at significantly lower levels in solar-withered leaves (SW) than in fresh leaves (FL) and indoor-withered leaves (IW). However, terpenoid, JA, and MeJA were present at a higher level in SW than FL and IW. By analyzing the transcriptome data, we obtained a total of 32,036 lncRNAs. On the basis of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, flavonoid metabolic pathway, terpenoid metabolic pathway, and JA/MeJA biosynthesis and signal transduction pathway were the representative pathways in this study. And a total of 63 differentially expressed-lncRNAs (DE-lncRNAs) and 23 target genes were identified in the 3 pathways. Analysis of the expression profiles of DE-lncRNAs and their target genes in SW compared with IW, we found that 4 up-regulated genes (FLS, CCR, CAD, and HCT), 7 up-regulated lncRNAs, 4 down-regulated genes (4CL, CHI, F3H, and F3'H), and 3 down-regulated lncRNAs in flavonoid metabolism; 9 up-regulated genes (DXS, CMK, HDS, HDR, AACT, MVK, PMK, GGPPS, and TPS), 3 up-regulated lncRNAs, 6 down-regulated lncRNAs in terpenoid metabolism; 6 up-regulated genes (LOX, AOS, AOC, OPR, ACX, and MFP2), 4 up-regulated lncRNAs, and 3 down-regulated lncRNAs in JA/MeJA biosynthesis and signal transduction pathway. Conclusions These results suggested that the expression of DE-lncRNAs and their targets involved in the 3 pathways maybe related to the low content of total flavonoid, total catechins, EGC, CG, GCG, ECG, and EGCG, and high content of terpenoid in SW. Moreover, solar light, high content of JA and MeJA, and the endogenous target mimics (eTMs) regulatory mechanism in SW were also crucial factors in increasing the terpenoid. These findings provide new insights into the view of "Kàn qīng shài qīng" that the solar-withering is more contribute to the high quality flavor of oolong tea compared to the indoor-withering.

pygopusencodes a nuclear protein essential for Wingless/Wnt signaling

Development ◽  
2002 ◽  
Vol 129 (17) ◽  
pp. 4089-4101 ◽  
Author(s):  
Tatyana Y. Belenkaya ◽  
Chun Han ◽  
Henrietta J. Standley ◽  
Xinda Lin ◽  
Douglas W. Houston ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Target Genes ◽  
Nuclear Protein ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Phd Finger ◽  
Nuclear Function ◽  
Evolutionarily Conserved ◽  
Wnt Signal

The Wingless (Wg)/Wnt signal transduction pathway regulates many developmental processes through a complex of Armadillo(Arm)/β-catenin and the HMG-box transcription factors of the Tcf family. We report the identification of a new component, Pygopus (Pygo), that plays an essential role in the Wg/Wnt signal transduction pathway. We show that Wg signaling is diminished during embryogenesis and imaginal disc development in the absence of pygo activity. Pygo acts downstream or in parallel with Arm to regulate the nuclear function of Arm protein. pygo encodes a novel and evolutionarily conserved nuclear protein bearing a PHD finger that is essential for its activity. We further show that Pygo can form a complex with Arm in vivo and possesses a transcription activation domain(s). Finally, we have isolated a Xenopus homolog of pygo (Xpygo). Depletion of maternal Xpygo by antisense deoxyoligonucleotides leads to ventralized embryonic defects and a reduction of the expression of Wnt target genes. Together, these findings demonstrate that Pygo is an essential component in the Wg/Wnt signal transduction pathway and is likely to act as a transcription co-activator required for the nuclear function of Arm/β-catenin.

The Dorsal-related immunity factor (Dif) can define the dorsal-ventral axis of polarity in the Drosophila embryo

Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 2159-2169 ◽  
Author(s):  
D. Stein ◽  
J.S. Goltz ◽  
J. Jurcsak ◽  
L. Stevens
Keyword(s):  
Signal Transduction ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Drosophila Embryo ◽  
Transduction Pathway ◽  
Homologous Proteins ◽  
Helix Loop Helix ◽  
Ability To Act ◽  
Egg Shell ◽  
Drosophila Embryos

In Drosophila embryos, dorsal-ventral polarity is defined by a signal transduction pathway that regulates nuclear import of the Dorsal protein. Dorsal protein's ability to act as a transcriptional activator of some zygotic genes and a repressor of others defines structure along the dorsal-ventral axis. Dorsal is a member of a group of proteins, the Rel-homologous proteins, whose activity is regulated at the level of nuclear localization. Dif, a more recently identified Drosophila Rel-homologue, has been proposed to act as a mediator of the immune response in Drosophila. In an effort to understand the function and regulation of Rel-homologous proteins in Drosophila, we have expressed Dif protein in Drosophila embryos derived from dorsal mutant mothers. We found that the Dif protein was capable of restoring embryonic dorsal-ventral pattern elements and was able to define polarity correctly with respect to the orientation of the egg shell. This, together with the observation that the ability of Dif to restore a dorsal-ventral axis depended on the signal transduction pathway that normally regulates Dorsal, suggests that Dif protein formed a nuclear concentration gradient similar to that seen for Dorsal. By studying the expression of Dorsal target genes we found that Dif could activate the zygotic genes that Dorsal activates and repress the genes repressed by Dorsal. Differences in the expression of these target genes, as well as the results from interaction studies carried out in yeast, suggest that Dif is not capable of synergizing with the basic helix-loop-helix transcription factors with which Dorsal normally interacts, and thereby lacks an important component of Dorsal-mediated pattern formation.

scholarly journals Dominant negative Ras enhances lactogenic hormone-induced differentiation by blocking activation of the Raf-Mek-Erk signal transduction pathway

2004 ◽  
Vol 201 (2) ◽  
pp. 244-258 ◽  
Author(s):  
Maria Grazia Cerrito ◽  
Traci Galbaugh ◽  
Weihan Wang ◽  
Treasa Chopp ◽  
David Salomon ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Dominant Negative ◽  
Transduction Pathway ◽  
Induced Differentiation ◽  
Lactogenic Hormone
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