scholarly journals A novel role for Ets4 in axis specification and cell migration in the spider Parasteatoda tepidariorum

2017 ◽  
Author(s):  
Matthias Pechmann ◽  
Matthew A. Benton ◽  
Nathan J. Kenny ◽  
Nico Posnien ◽  
Siegfried Roth
Keyword(s):  
Embryonic Development ◽  
Cell Fate ◽  
Ectopic Expression ◽  
Specific Gene ◽  
Dorsoventral Patterning ◽  
Embryonic Axes ◽  
Parasteatoda Tepidariorum ◽  
Spemann Organizer ◽  
Secondary Axis ◽  
And Migration

AbstractOrganizers play important roles during the embryonic development of many animals. The most famous example is the Spemann organizer that sets up embryonic axes in amphibian embryos.In spiders, a group of BMP secreting mesenchymal cells (the cumulus) functions as an organizer of the dorsoventral axis. Similar to experiments performed with the Spemann organizer, transplantation of the cumulus is able to induce a secondary axis in spiders.Despite the importance of this structure, it is unknown which factors are needed to activate cumulus specific gene expression.To address this question, we performed a transcriptomic analysis of early embryonic development in the spider Parasteatoda tepidariorum. Through this work, we found that the transcription factor Pt-Ets4 is needed for cumulus integrity, dorsoventral patterning and for the activation of Pt-hunchback and Pt-twist expression. Furthermore, ectopic expression of Pt-Ets4 is sufficient to induce cell delamination and migration by inducing a mesoderm-like cell fate.

scholarly journals A novel role for Ets4 in axis specification and cell migration in the spider Parasteatoda tepidariorum

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Matthias Pechmann ◽  
Matthew A Benton ◽  
Nathan J Kenny ◽  
Nico Posnien ◽  
Siegfried Roth
Keyword(s):  
Embryonic Development ◽  
Cell Fate ◽  
Ectopic Expression ◽  
Specific Gene ◽  
Embryonic Axes ◽  
Parasteatoda Tepidariorum ◽  
Spemann Organizer ◽  
Secondary Axis ◽  
Twist Expression ◽  
And Migration

Organizers play important roles during the embryonic development of many animals. The most famous example is the Spemann organizer that sets up embryonic axes in amphibian embryos. In spiders, a group of BMP secreting mesenchymal cells (the cumulus) functions as an organizer of the dorsoventral axis. Similar to experiments performed with the Spemann organizer, transplantation of the cumulus is able to induce a secondary axis in spiders. Despite the importance of this structure, it is unknown which factors are needed to activate cumulus specific gene expression. To address this question, we performed a transcriptomic analysis of early embryonic development in the spider Parasteatoda tepidariorum. Through this work, we found that the transcription factor Pt-Ets4 is needed for cumulus integrity, dorsoventral patterning and for the activation of Pt-hunchback and Pt-twist expression. Furthermore, ectopic expression of Pt-Ets4 is sufficient to induce cell delamination and migration by inducing a mesoderm-like cell fate.

Identifying targets of the rough homeobox gene of Drosophila: evidence that rhomboid functions in eye development

Development ◽  
1992 ◽  
Vol 116 (2) ◽  
pp. 335-346 ◽  
Author(s):  
M. Freeman ◽  
B.E. Kimmel ◽  
G.M. Rubin
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Eye Development ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Homeodomain Protein ◽  
Dorsoventral Patterning ◽  
Altered Expression ◽  
Enhancer Trap Lines

In order to identify potential target genes of the rough homeodomain protein, which is known to specify some aspects of the R2/R5 photoreceptor subtype in the Drosophila eye, we have carried out a search for enhancer trap lines whose expression is rough-dependent. We crossed 101 enhancer traps that are expressed in the developing eye into a rough mutant background, and have identified seven lines that have altered expression patterns. One of these putative rough target genes is rhomboid, a gene known to be required for dorsoventral patterning and development of some of the nervous system in the embryo. We have examined the role of rhomboid in eye development and find that, while mutant clones have only a subtle phenotype, ectopic expression of the gene causes the non-neuronal mystery cells to be transformed into photoreceptors. We propose that rhomboid is a part of a partially redundant network of genes that specify photoreceptor cell fate.

Regulation of Spemann organizer formation by the intracellular kinase Xgsk-3

Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 755-765 ◽  
Author(s):  
S.B. Pierce ◽  
D. Kimelman
Keyword(s):  
Ectopic Expression ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Axis Formation ◽  
Serine Threonine Kinase ◽  
Spemann Organizer ◽  
Isolation And Characterization ◽  
Secondary Axis ◽  
Dorsal Axis ◽  
Negative Effect

Dorsal axis formation in the Xenopus embryo can be induced by the ectopic expression of several Wnt family members. In Drosophila, the protein encoded by the Wnt family gene, wingless, signals through a pathway that antagonizes the effects of the serine/threonine kinase zeste-white 3/shaggy. We describe the isolation and characterization of a Xenopus homolog of zeste-white 3/shaggy, Xgsk-3. A kinase-dead mutant of Xgsk-3, Xgsk-3K-->R, has a dominant negative effect and mimics the ability of Wnt to induce a secondary axis by induction of an ectopic Spemann organizer. Xgsk-3K-->R, like Wnt, induces dorsal axis formation when expressed in the deep vegetal cells, which do not contribute to the axis. These results indicate that the dorsal fate is actively repressed by Xgsk-3, which must be inactivated for dorsal axis formation to occur. Furthermore, our work suggests that the effects of Xgsk-3K-->R are mediated by an additional intercellular signal.

Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2687-2700 ◽  
Author(s):  
M.A. Deardorff ◽  
C. Tan ◽  
L.J. Conrad ◽  
P.S. Klein
Keyword(s):  
Ectopic Expression ◽  
Axis Formation ◽  
Vertebrate Development ◽  
Spemann Organizer ◽  
Secondary Axis ◽  
Wnt Ligands ◽  
Endogenous Role ◽  
Dorsal Cells ◽  
Wnt Signal

Wnts are secreted signaling molecules implicated in a large number of developmental processes. Frizzled proteins have been identified as likely receptors for Wnt ligands in vertebrates and invertebrates, but a functional role for vertebrate frizzleds has not yet been defined. To assess the endogenous role of frizzled proteins during vertebrate development, we have identified and characterized a Xenopus frizzled gene (xfz8). It is highly expressed in the deep cells of the Spemann organizer prior to dorsal lip formation and in the early involuting marginal zone. Ectopic expression of xfz8 in ventral cells leads to complete secondary axis formation and can synergize with Xwnt-8 while an inhibitory form of xfz8 (Nxfz8) blocks axis duplication by Xwnt-8, consistent with a role for xfz8 in Wnt signal transduction. Expression of Nxfz8 in dorsal cells has profound effects on morphogenesis during gastrulation and neurulation that result in dramatic shortening of the anterior-posterior axis. Our results suggest a role for xfz8 in morphogenesis during the gastrula stage of embryogenesis.

A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4253-4264 ◽  
Author(s):  
M. Furthauer ◽  
C. Thisse ◽  
B. Thisse
Keyword(s):  
Ectopic Expression ◽  
Ventral Part ◽  
Dorsoventral Patterning ◽  
Blastula Stage ◽  
Dorsoventral Axis ◽  
Spemann's Organizer ◽  
Secondary Axis ◽  
Vertebrate Embryo

Signals released from Spemann's organizer, together with ventralizing factors such as BMPs, are necessary to pattern the dorsoventral axis of the vertebrate embryo. We report that a member of the FGF family, fgf-8, not secreted by the axial mesoderm but expressed in a dorsoventral gradient at the margin of the zebrafish gastrula, also contributes to the establishment of the dorsoventral axis of the embryo. Ectopic expression of FGF-8 leads to the expansion of dorsolateral derivatives at the expense of ventral and posterior domains. Moreover, FGF-8 displays some organizer properties as it induces the formation of a partial secondary axis in the absence of factors released from Spemann's organizer territory. Analysis of its interaction with the ventralizing factors, BMPs, reveals that overexpression of FGF-8 inhibits the expression of these factors in the ventral part of the embryo as early as blastula stage, suggesting that FGF-8 acts upstream of BMP2 and BMP4. We conclude that FGF-8 is involved in defining dorsoventral identity and is an important organizing factor responsible for specification of mesodermal and ectodermal dorsolateral territories of the zebrafish gastrula.

scholarly journals Ciglitazone—a human PPARγ agonist—disrupts dorsoventral patterning in zebrafish

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8054 ◽  
Author(s):  
Vanessa Cheng ◽  
Subham Dasgupta ◽  
Aalekhya Reddam ◽  
David C. Volz
Keyword(s):  
Embryonic Development ◽  
Cell Fate ◽  
De Novo ◽  
Early Embryonic Development ◽  
Zebrafish Embryos ◽  
Peroxisome Proliferator ◽  
Dorsoventral Patterning ◽  
Peroxisome Proliferator Activated Receptor ◽  
Critical Window ◽  
Pparγ Agonist

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that regulates lipid/glucose homeostasis and adipocyte differentiation. While the role of PPARγ in adipogenesis and diabetes has been extensively studied, little is known about PPARγ function during early embryonic development. Within zebrafish, maternally-loaded pparγ transcripts are present within the first 6 h post-fertilization (hpf), and de novo transcription of zygotic pparγ commences at ~48 hpf. Since maternal pparγ transcripts are elevated during a critical window of cell fate specification, the objective of this study was to test the hypothesis that PPARγ regulates gastrulation and dorsoventral patterning during zebrafish embryogenesis. To accomplish this objective, we relied on (1) ciglitazone as a potent PPARγ agonist and (2) a splice-blocking, pparγ-specific morpholino to knockdown pparγ. We found that initiation of ciglitazone—a potent human PPARγ agonist—exposure by 4 hpf resulted in concentration-dependent effects on dorsoventral patterning in the absence of epiboly defects during gastrulation, leading to ventralized embryos by 24 hpf. Interestingly, ciglitazone-induced ventralization was reversed by co-exposure with dorsomorphin, a bone morphogenetic protein signaling inhibitor that induces strong dorsalization within zebrafish embryos. Moreover, mRNA-sequencing revealed that lipid- and cholesterol-related processes were affected by exposure to ciglitazone. However, pparγ knockdown did not block ciglitazone-induced ventralization, suggesting that PPARγ is not required for dorsoventral patterning nor involved in ciglitazone-induced toxicity within zebrafish embryos. Our findings point to a novel, PPARγ-independent mechanism of action and phenotype following ciglitazone exposure during early embryonic development.

Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 4107-4119 ◽  
Author(s):  
A. Duggan ◽  
C. Ma ◽  
M. Chalfie
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Binding Sites ◽  
Ectopic Expression ◽  
The Body ◽  
Specific Gene ◽  
Homeodomain Protein ◽  
Activation Domains ◽  
Cell Lineages

The nematode Caenorhabditis elegans possesses six morphologically similar neurons that are responsible for sensing gentle touch to the body. Previous genetic studies identified genes that are necessary for the production and differentiation of these touch cells. In particular, unc-86 encodes a POU-type homeodomain protein needed for the production of the touch cells, while mec-3 encodes a LIM-type homeodomain protein needed for the differentiation of the touch cells. Molecular studies showed that MEC-3 and UNC-86 bind cooperatively to sites in the mec-3 promoter and can synergistically activate transcription from it in vitro. Here we show that UNC-86::MEC-3 hetero-oligomer-binding sites are also found in the promoters of two presumed targets of mec-3, the mec-4 and mec-7 genes, that are necessary for the function of the touch cells. These sites, which are well-conserved in the related nematode C. briggsae, are required for promoter activity. When one of the binding sites is cloned into a heterologous promoter, expression is found in the touch cells and two to four other cells that express mec-3 and unc-86. These data support a model in which touch-cell differentiation is specified, in part, by the UNC-86::MEC-3 hetero-oligomer and not by MEC-3 alone. Ectopic expression of mec-3, driven by a heat-shock promoter, also supports this hypothesis: the acquisition of touch-cell characteristics by several additional cells under these conditions required unc-86. Since the touch-cell lineages express UNC-86 before MEC-3, MEC-3 appears to modify the activity of UNC-86, leading to touch-cell-specific gene expression. Because both UNC-86 and MEC-3 have activation domains, the formation of the hetero-oligomer may create a strong activator. In the modification of UNC-86 function by MEC-3 in the touch cells, these studies provide an example of how the sequential activation of transcription factors can determine cell fate within particular cell lineages.

scholarly journals Inhibition of Cyclooxygenase-2 Alters Craniofacial Patterning during Early Embryonic Development of Chick

2021 ◽  
Vol 9 (2) ◽  
pp. 16
Author(s):  
Bhaval Parmar ◽  
Urja Verma ◽  
Kashmira Khaire ◽  
Dhanush Danes ◽  
Suresh Balakrishnan
Keyword(s):  
Embryonic Development ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Neural Crest Cell ◽  
Cyclooxygenase 2 ◽  
Nuclear Antigen ◽  
Chick Embryos ◽  
Downstream Effector ◽  
Cox 2 ◽  
And Migration

A recent study from our lab revealed that the inhibition of cyclooxygenase-2 (COX-2) exclusively reduces the level of PGE2 (Prostaglandin E2) among prostanoids and hampers the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence cranial neural crest cell (CNCC) migration was checked in chick embryos after inhibiting COX-2 activity using etoricoxib. The compromised level of cell adhesion molecules and their upstream regulators, namely CDH1 (E-cadherin), CDH2 (N-cadherin), MSX1 (Msh homeobox 1), and TGF-β (Transforming growth factor beta), observed in the etoricoxib-treated embryos indicate that COX-2, through its downstream effector PGE2, regulates the expression of these factors perhaps to aid the migration of CNCCs. The histological features and levels of FoxD3 (Forkhead box D3), as well as PCNA (Proliferating cell nuclear antigen), further consolidate the role of COX-2 in the migration and survival of CNCCs in developing embryos. The results of the current study indicate that COX-2 plays a pivotal role in orchestrating craniofacial structures perhaps by modulating CNCC proliferation and migration during the embryonic development of chicks.

scholarly journals Crosstalk between MUC1 and VEGF in angiogenesis and metastasis: a review highlighting roles of the MUC1 with an emphasis on metastatic and angiogenic signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Farnaz Khodabakhsh ◽  
Parnaz Merikhian ◽  
Mohammad Reza Eisavand ◽  
Leila Farahmand
Keyword(s):  
Tumor Growth ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Endothelial Cell Proliferation ◽  
Mucin 1 ◽  
Signaling Transduction ◽  
Growth And Survival ◽  
Angiogenic Proteins ◽  
Angiogenic Effect ◽  
And Migration

AbstractVEGF and its receptor family (VEGFR) members have unique signaling transduction system that play significant roles in most pathological processes, such as angiogenesis in tumor growth and metastasis. VEGF-VEGFR complex is a highly specific mitogen for endothelial cells and any de-regulation of the angiogenic balance implicates directly in endothelial cell proliferation and migration. Moreover, it has been shown that overexpressing Mucin 1 (MUC1) on the surface of many tumor cells resulting in upregulation of numerous signaling transduction cascades, such as growth and survival signaling pathways related to RTKs, loss of cell-cell and cell-matrix adhesion, and EMT. It promotes gene transcription of pro-angiogenic proteins such as HIF-1α during periods of oxygen scarcity (hypoxia) to enhance tumor growth and angiogenesis stimulation. In contrast, the cytoplasmic domain of MUC1 (MUC1-C) inhibits apoptosis, which in turn, impresses upon cell fate. Besides, it has been established that reduction in VEGF expression level correlated with silencing MUC1-C level indicating the anti-angiogenic effect of MUC1 downregulation. This review enumerates the role of MUC1-C oncoprotein and VEGF in angiogenesis and metastasis and describes several signaling pathways by which MUC1-C would mediate the pro-angiogenic activities of cancer cells.

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