scholarly journals Interactions between 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Hypoxia Signaling Pathways in Zebrafish: Hypoxia Decreases Responses to TCDD in Zebrafish Embryos

2004 ◽  
Vol 78 (1) ◽  
pp. 68-77 ◽  
Author(s):  
A. L. Prasch
Keyword(s):  
Signaling Pathways ◽  
Zebrafish Embryos ◽  
Tetrachlorodibenzo P Dioxin ◽  
Hypoxia Signaling

scholarly journals When Wnts antagonize Wnts

2003 ◽  
Vol 162 (5) ◽  
pp. 753-756 ◽  
Author(s):  
Gilbert Weidinger ◽  
Randall T. Moon
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Limb Bud ◽  
Zebrafish Embryos ◽  
Previous Hypothesis ◽  
Distal Mouse ◽  
Wnt Ligands ◽  
Mouse Limb ◽  
Ectopic Activation ◽  
Canonical Wnt

Secreted Wnt ligands appear to activate a variety of signaling pathways. Two papers in this issue now present genetic evidence that “noncanonical” Wnt signaling inhibits the “canonical” Wnt/β-catenin pathway. Westfall et al. (2003a) show that zebrafish embryos lacking maternal Wnt-5 function are dorsalized due to ectopic activation of β-catenin, whereas Topol et al. (2003) report that chondrogenesis in the distal mouse limb bud depends on inhibition of Wnt/β-catenin signaling by a paralogue of Wnt-5. These studies present the first genetic confirmation of the previous hypothesis that vertebrate Wnt signaling pathways can act in an antagonistic manner.

scholarly journals Cessation of contraction induces cardiomyocyte remodeling during zebrafish cardiogenesis

2014 ◽  
Vol 306 (3) ◽  
pp. H382-H395 ◽  
Author(s):  
Jingchun Yang ◽  
Katherine A. Hartjes ◽  
Timothy J. Nelson ◽  
Xiaolei Xu
Keyword(s):  
Signaling Pathways ◽  
Heart Development ◽  
Myosin Ii ◽  
Cardiac Contraction ◽  
Zebrafish Embryos ◽  
Mechanical Forces ◽  
In Vivo Animal Model ◽  
Lateral Fusion ◽  
Phosphoinositide 3 Kinase

Contraction regulates heart development via a complex mechanotransduction process controlled by various mechanical forces. Here, we exploit zebrafish embryos as an in vivo animal model to discern the contribution from different mechanical forces and identify the underlying mechanotransductive signaling pathways of cardiogenesis. We treated 2 days postfertilization zebrafish embryos with Blebbistatin, a myosin II inhibitor, to stop cardiac contraction, which induces a response termed cessation of contraction-induced cardiomyocyte (CM) enlargement (CCE). Accompanying the CCE, lateral fusion of myofibrils was attenuated within CMs. The CCE can be blunted by loss of blood in tail-docked zebrafish but not in cloche mutant fish, suggesting that transmural pressure rather than shear stress is accountable for the chamber enlargement. By screening a panel of small molecule inhibitors, our data suggested essential functions of phosphoinositide 3-kinase signaling and protein synthesis in CCE, which are independent of the sarcomere integrity. In summary, we defined a unique CCE response in genetically tractable zebrafish embryos. A panel of assays was established to verify the contribution from extrinsic forces and interrogate underlying signaling pathways.

scholarly journals The Nuclear Export Inhibitor Selinexor Inhibits Hypoxia Signaling Pathways And 3D Spheroid Growth Of Cancer Cells

2019 ◽  
Vol Volume 12 ◽  
pp. 8387-8399
Author(s):  
Reinhard Depping ◽  
Moritz von Fallois ◽  
Yosef Landesman ◽  
Friederike Katharina Kosyna
Keyword(s):  
Cancer Cells ◽  
Signaling Pathways ◽  
Nuclear Export ◽  
Spheroid Growth ◽  
Hypoxia Signaling

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Disrupts Control of Cell Proliferation and Apoptosis in a Human Model of Adult Liver Progenitors

2019 ◽  
Vol 172 (2) ◽  
pp. 368-384
Author(s):  
Jana Svobodová ◽  
Jiřina Procházková ◽  
Markéta Kabátková ◽  
Martin Krkoška ◽  
Lenka Šmerdová ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathways ◽  
Human Model ◽  
Binding Motif ◽  
Adult Liver ◽  
Altered Expression ◽  
Heparg Cells ◽  
Induction Of Apoptosis ◽  
Tetrachlorodibenzo P Dioxin ◽  
The Impact

Abstract The aryl hydrocarbon receptor (AhR) activation has been shown to alter proliferation, apoptosis, or differentiation of adult rat liver progenitors. Here, we investigated the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated AhR activation on a human model of bipotent liver progenitors, undifferentiated HepaRG cells. We used both intact undifferentiated HepaRG cells, and the cells with silenced Hippo pathway effectors, yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), which play key role(s) in tissue-specific progenitor cell self-renewal and expansion, such as in liver, cardiac, or respiratory progenitors. TCDD induced cell proliferation in confluent undifferentiated HepaRG cells; however, following YAP, and, in particular, double YAP/TAZ knockdown, TCDD promoted induction of apoptosis. These results suggested that, unlike in mature hepatocytes, or hepatocyte-like cells, activation of the AhR may sensitize undifferentiated HepaRG cells to apoptotic stimuli. Induction of apoptosis in cells with silenced YAP/TAZ was associated with upregulation of death ligand TRAIL, and seemed to involve both extrinsic and mitochondrial apoptosis pathways. Global gene expression analysis further suggested that TCDD significantly altered expression of constituents and/or transcriptional targets of signaling pathways participating in control of expansion or differentiation of liver progenitors, including EGFR, Wnt/β-catenin, or tumor growth factor-β signaling pathways. TCDD significantly upregulated cytosolic proapoptotic protein BMF (Bcl-2 modifying factor) in HepaRG cells, which could be linked with an enhanced sensitivity of TCDD-treated cells to apoptosis. Our results suggest that, in addition to promotion of cell proliferation and alteration of signaling pathways controlling expansion of human adult liver progenitors, AhR ligands may also sensitize human liver progenitor cells to apoptosis.

Peli1b governs the brain patterning via ERK signaling pathways in zebrafish embryos

Gene ◽  
2019 ◽  
Vol 694 ◽  
pp. 1-6 ◽  
Author(s):  
Ajeet Kumar ◽  
Mrudhula Anuppalle ◽  
Sateesh Maddirevula ◽  
Tae-Lin Huh ◽  
Joonho Choe ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Erk Signaling ◽  
Zebrafish Embryos ◽  
The Brain ◽  
Brain Patterning

scholarly journals Small Molecule Screening in Zebrafish Embryos Identifies Signaling Pathways Regulating Early Thyroid Development

2019 ◽  
Author(s):  
Benoit Haerlingen ◽  
Robert Opitz ◽  
Isabelle Vandernoot ◽  
Achim Trubiroha ◽  
Pierre Gillotay ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Model Organisms ◽  
Thyroid Cell ◽  
Zebrafish Embryos ◽  
Cardiovascular Development ◽  
Drug Induced ◽  
Thyroid Development

AbstractBackgroundDefects in embryonic development of the thyroid gland are a major cause for congenital hypothyroidism in human newborns but the underlying molecular mechanisms are still poorly understood. Organ development relies on a tightly regulated interplay between extrinsic signaling cues and cell intrinsic factors. At present, however, there is limited knowledge about the specific extrinsic signaling cues that regulate foregut endoderm patterning, thyroid cell specification and subsequent morphogenetic processes in thyroid development.MethodsTo begin to address this problem in a systematic way, we used zebrafish embryos to perform a series of in vivo phenotype-driven chemical genetic screens to identify signaling cues regulating early thyroid development. For this purpose, we treated zebrafish embryos during different developmental periods with a panel of small molecule compounds known to manipulate the activity of major signaling pathways and scored phenotypic deviations in thyroid, endoderm and cardiovascular development using whole mount in situ hybridization and transgenic fluorescent reporter models.ResultsSystematic assessment of drugged embryos recovered a range of thyroid phenotypes including expansion, reduction or lack of the early thyroid anlage, defective thyroid budding as well as hypoplastic, enlarged or overtly disorganized presentation of the thyroid primordium after budding. Our pharmacological screening identified BMP and FGF signaling as key factors for thyroid specification and early thyroid organogenesis, highlight the importance of low Wnt activities during early development for thyroid specification and implicate drug-induced cardiac and vascular anomalies as likely indirect mechanisms causing various forms of thyroid dysgenesis.ConclusionsBy integrating the outcome of our screening efforts with previously available information from other model organisms including Xenopus, chicken and mouse, we conclude that signaling cues regulating thyroid development appear broadly conserved across vertebrates. We therefore expect that observations made in zebrafish can inform mammalian models of thyroid organogenesis to further our understanding of the molecular mechanisms of congenital thyroid diseases.

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