Determination of wing cell fate by the escargot and snail genes in Drosophila

Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1059-1067 ◽  
Author(s):  
N. Fuse ◽  
S. Hirose ◽  
S. Hayashi
Keyword(s):  
Cell Fate ◽  
Double Mutant ◽  
Target Genes ◽  
Shape Change ◽  
Wing Disc ◽  
Specific Cell ◽  
Wing Development ◽  
Specific Expression ◽  
Snail Expression ◽  
Wing Cell

Inset appendages such as the wing and the leg are formed in response to inductive signals in the embryonic field. In Drosophila, cells receiving such signals initiate developmental programs which allow them to become imaginal discs. Subsequently, these discs autonomously organize patterns specific for each appendage. We here report that two related transcription factors, Escargot and Snail that are expressed in the embryonic wing disc, function as intrinsic determinants of the wing cell fate. In escargot or snail mutant embryos, wing-specific expression of Snail, Vestigial and beta-galactosidase regulated by escargot enhancer were found as well as in wild-type embryos. However, in escargot snail double mutant embryos, wing development proceeded until stage 13, but the marker expression was not maintained in later stages, and the invagination of the primordium was absent. From such analyses, it was concluded that Escargot and Snail expression in the wing disc are maintained by their auto- and crossactivation. Ubiquitous escargot or snail expression induced from the hsp70 promoter rescued the escargot snail double mutant phenotype with the effects confined to the prospective wing cells. Similar DNA binding specificities of Escargot and Snail suggest that they control the same set of genes required for wing development. We thus propose the following scenario for early wing disc development. Prospective wing cells respond to the induction by turning on escargot and snail transcription, and become competent for regulation by Escargot and Snail. Such cells initiate auto- and crossregulatory circuits of escargot and snail. The sustained Escargot and Snail expression then activates vestigial and other target genes that are essential for wing development. This maintains the commitment to the wing cell fate and induces wing-specific cell shape change.

scholarly journals Predicting cell-cycle expressed genes identifies canonical and non-canonical regulators of time-specific expression in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Nicholas L Panchy ◽  
John P. Lloyd ◽  
Shin-Han Shiu
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Target Genes ◽  
Specific Cell ◽  
Data Sets ◽  
Cell Cycle Regulators ◽  
Specific Expression ◽  
Regulatory Data ◽  
Time Specific ◽  
Cycle Regulation

AbstractThe collection all TFs, target genes and their interactions in an organism form a gene regulatory network (GRN), which underly complex patterns of transcription even in unicellular species. However, identifying which interactions regulate expression in a specific temporal context remains a challenging task. With multiple experimental and computational approaches to characterize GRNs, we predicted general and phase-specific cell-cycle expression in Saccharomyces cerevisiae using four regulatory data sets: chromatin immunoprecipitation (ChIP), TF deletion data (Deletion), protein binding microarrays (PBMs), and position weight matrices (PWMs). Our results indicate that the source of regulatory interaction information significantly impacts our ability to predict cell-cycle expression where the best model was constructed by combining selected TF features from ChIP and Deletion data as well as TF-TF interaction features in the form of feed-forward loops. The TFs that were the best predictors of cell-cycle expression were enriched for known cell-cycle regulators but also include regulators not implicated in cell-cycle regulation previously. In addition, ChIP and Deletion datasets led to the identification different subsets of TFs important for predicting cell-cycle expression. Finally, analysis of important TF-TF interaction features suggests that the GRN regulating cell cycle expression is highly interconnected and clustered around four groups of genes, two of which represent known cell-cycle regulatory complexes, while the other two contain TFs that are not known cell-cycle regulators (Ste12-Tex1 and Rap1-Hap1-Msn4), but are nonetheless important to regulating the timing of expression. Thus, not only do our models accurately reflect what is known about the regulation of the S. cerevisiae cell cycle, they can be used to discover regulatory factors which play a role in controlling expression during the cell cycle as well as other contexts with discrete temporal patterns of expression.

scholarly journals Control of skeletal morphogenesis by the Hippo-YAP/TAZ pathway

Development ◽  
2020 ◽  
Vol 147 (21) ◽  
pp. dev187187
Author(s):  
Hannah K. Vanyai ◽  
Fabrice Prin ◽  
Oriane Guillermin ◽  
Bishara Marzook ◽  
Stefan Boeing ◽  
...  
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Control Cell ◽  
Tissue Growth ◽  
Double Knockout ◽  
Cartilage Growth ◽  
Chondrocyte Proliferation ◽  
Specific Expression

ABSTRACTThe Hippo-YAP/TAZ pathway is an important regulator of tissue growth, but can also control cell fate or tissue morphogenesis. Here, we investigate the function of the Hippo pathway during the development of cartilage, which forms the majority of the skeleton. Previously, YAP was proposed to inhibit skeletal size by repressing chondrocyte proliferation and differentiation. We find that, in vitro, Yap/Taz double knockout impairs murine chondrocyte proliferation, whereas constitutively nuclear nls-YAP5SA accelerates proliferation, in line with the canonical role of this pathway in most tissues. However, in vivo, cartilage-specific knockout of Yap/Taz does not prevent chondrocyte proliferation, differentiation or skeletal growth, but rather results in various skeletal deformities including cleft palate. Cartilage-specific expression of nls-YAP5SA or knockout of Lats1/2 do not increase cartilage growth, but instead lead to catastrophic malformations resembling chondrodysplasia or achondrogenesis. Physiological YAP target genes in cartilage include Ctgf, Cyr61 and several matrix remodelling enzymes. Thus, YAP/TAZ activity controls chondrocyte proliferation in vitro, possibly reflecting a regenerative response, but is dispensable for chondrocyte proliferation in vivo, and instead functions to control cartilage morphogenesis via regulation of the extracellular matrix.

scholarly journals Arkadia via SNON enables NODAL-SMAD2/3 signaling effectors to transcribe different genes depending on their levels

2018 ◽  
Author(s):  
Jonathon M. Carthy ◽  
Marilia Ioannou ◽  
Vasso Episkopou
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Embryonic Stem ◽  
Null Mouse ◽  
Specific Cell ◽  
Cell Fates ◽  
Mammalian Embryo ◽  
Cell Fate Decisions ◽  
Dependent Cell ◽  
Anterior Posterior

AbstractHow cells assess levels of signaling and select to transcribe different target genes depending on the levels of activated effectors remains elusive. High NODAL-signalling levels specify anterior/head, lower specify posterior, and complete loss abolishes anterior-posterior patterning in the mammalian embryo. Here we show that cells assess NODAL-activated SMAD2 and SMAD3 (SMAD2/3) effector-levels by complex formation and pairing each effector with the co-repressor SNON, which is present in the cell before signaling. These complexes enable the E3-ubiquitin ligase Arkadia (RNF111) to degrade SNON. High SMAD2/3 levels can saturate and remove SNON, leading to derepression and activation of a subset of targets (high targets) that are highly susceptible to SNON repression. However, low SMAD2/3 levels can only reduce SNON preventing derepression/activation of high targets. Arkadia degrades SNON transiently only upon signaling exposure, leading to dynamic signaling-responses, which most likely initiate level-specific cell-fate decisions. Arkadia-null mouse embryos and Embryonic Stem Cells (ESC) cannot develop anterior tissues and head. However, SnoN/Arkadia, double-null embryos and ESCs are rescued confirming that Arkadia removes SNON, to achieve level-dependent cell-fatesOne Sentence SummarySignaling intensity induces equivalent degradation of a transcriptional repressor leading to level-dependent responses.

scholarly journals At a Crossroads to Cancer: How p53-induced Cell Fate Decisions Secure Genome Integrity

2021 ◽  
Author(s):  
Dario Rizzotto ◽  
Lukas Englmaier ◽  
Andreas Villunger
Keyword(s):  
Cell Death ◽  
Cell Fate ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Current Knowledge ◽  
Cellular Transformation ◽  
Model Systems ◽  
Specific Cell ◽  
Cell Type ◽  
Cell Fate Decisions

P53 is known as the most critical tumor suppressor and is often referred to as the guardian of our genome. More than 40 years after its discovery, we are still struggling to understand all molecular details on how this transcription factor prevents oncogenesis or how to leverage current knowledge about its function to improve cancer treatment. Multiple cues, including DNA-damage or mitotic errors, can lead to the stabilization and nuclear translocation of p53, initiating the expression of multiple target genes. These transcriptional programs may well be cell type and stimulus-specific, as is their outcome that ultimately imposes a barrier to cellular transformation. Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered as critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview on multiple ways how p53 can trigger cell death. We argue that a comparative analysis of different types of p53 responses, elicited by different triggers in a time-resolved manner in well-defined model systems is critical to understand cell type specific cell fate induced by p53 upon its activation, in order to resolve the remaining mystery of its tumor suppressive function.

scholarly journals Anchor negatively regulates BMP signaling to control Drosophila wing development

2016 ◽  
Author(s):  
Xiaochun Wang ◽  
Ziguang Liu ◽  
Li hua Jin
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Pupal Stage ◽  
Wing Disc ◽  
Bmp Signaling ◽  
Wing Development ◽  
The Novel ◽  
Vein Formation ◽  
Summary Statement ◽  
Wing Discs

ABSTRACTSummary statementThe novel gene anchor is the ortholog of vertebrate GPR155, which contributes to preventing wing disc tissue overgrowth and limiting the phosphorylation of Mad in presumptive veins during the pupal stage.G protein-coupled receptors play a particularly important function in many organisms. The novel Drosophila gene anchor is the ortholog of vertebrate GPR155, and its molecular function and biological process are not yet known, especially in wing development. Knocking down anchor resulted in increased wing size and extra and thickened veins. These abnormal wing phenotypes are similar to those observed in gain-of-function of BMP signaling experiments. We observed that the BMP signaling indicator p-Mad was significantly increased in anchor RNAi-induced wing discs in larvae and that it also abnormally accumulated in intervein regions in pupae. Furthermore, the expression of BMP signaling pathway target genes were examined using a lacZ reporter, and the results indicated that omb and sal were substantially increased in anchor knockdown wing discs. In a study of genetic interactions between Anchor and BMP signaling pathway, the broadened and ectopic vein tissues were rescued by knocking down BMP levels. The results suggested that the function of Anchor is to negatively regulate BMP signaling during wing development and vein formation, and that Anchor targets or works upstream of Dpp.

scholarly journals At a Crossroads to Cancer: How p53-Induced Cell Fate Decisions Secure Genome Integrity

2021 ◽  
Vol 22 (19) ◽  
pp. 10883
Author(s):  
Dario Rizzotto ◽  
Lukas Englmaier ◽  
Andreas Villunger
Keyword(s):  
Cell Death ◽  
Cell Fate ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Current Knowledge ◽  
Cellular Transformation ◽  
Model Systems ◽  
Specific Cell ◽  
Cell Type ◽  
Cell Fate Decisions

P53 is known as the most critical tumor suppressor and is often referred to as the guardian of our genome. More than 40 years after its discovery, we are still struggling to understand all molecular details on how this transcription factor prevents oncogenesis or how to leverage current knowledge about its function to improve cancer treatment. Multiple cues, including DNA-damage or mitotic errors, can lead to the stabilization and nuclear translocation of p53, initiating the expression of multiple target genes. These transcriptional programs may be cell-type- and stimulus-specific, as is their outcome that ultimately imposes a barrier to cellular transformation. Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview of multiple ways that p53 can trigger cell death. We argue that a comparative analysis of different types of p53 responses, elicited by different triggers in a time-resolved manner in well-defined model systems, is critical to understand the cell-type-specific cell fate induced by p53 upon its activation in order to resolve the remaining mystery of its tumor-suppressive function.

TONDU (TDU), a novel human protein related to the product of vestigial (vg) gene of Drosophila melanogaster interacts with vertebrate TEF factors and substitutes for Vg function in wing formation

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4807-4816 ◽  
Author(s):  
P. Vaudin ◽  
R. Delanoue ◽  
I. Davidson ◽  
J. Silber ◽  
A. Zider
Keyword(s):  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Wing Disc ◽  
Human Protein ◽  
Wing Development ◽  
Dna Binding Domain ◽  
Activation Domains ◽  
Wing Formation ◽  
Transcriptional Activation Domains

The mammalian TEF and the Drosophila scalloped genes belong to a conserved family of transcriptional factors that possesses a TEA/ATTS DNA-binding domain. Transcriptional activation by these proteins likely requires interactions with specific coactivators. In Drosophila, Scalloped (Sd) interacts with Vestigial (Vg) to form a complex, which binds DNA through the Sd TEA/ATTS domain. The Sd-Vg heterodimer is a key regulator of wing development, which directly controls several target genes and is able to induce wing outgrowth when ectopically expressed. Here we show that Vg contains two distinct transcriptional activation domains, suggesting that the function of Vg is to mediate transcriptional activation by Sd. By expressing a chimeric GAL4-Sd protein in Drosophila, we found that the transcriptional activity of the Vg-Sd heterodimer is negatively regulated at the AP and DV boundary of the wing disc. We also identify a novel human protein, TONDU, which contains a short domain homologous to the domain of Vg required for interaction with Sd. We show that TONDU specifically interacts with a domain conserved in all the mammalian TEF factors. Expression of TDU in Drosophila by means of the UAS-GAL4 system shows that this human protein can substitute for Vg in wing formation. We propose that TDU is a specific coactivator for the mammalian TEFs.

scholarly journals IκBα targeting promotes oxidative stress-dependent cell death

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Giovanna Carrà ◽  
Giuseppe Ermondi ◽  
Chiara Riganti ◽  
Luisella Righi ◽  
Giulia Caron ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Protein Interactions ◽  
In Silico ◽  
Inverse Correlation ◽  
Ros Production ◽  
Gene Encoding ◽  
Specific Expression ◽  
Novel Approach ◽  
Stress Dependent

Abstract Background Oxidative stress is a hallmark of many cancers. The increment in reactive oxygen species (ROS), resulting from an increased mitochondrial respiration, is the major cause of oxidative stress. Cell fate is known to be intricately linked to the amount of ROS produced. The direct generation of ROS is also one of the mechanisms exploited by common anticancer therapies, such as chemotherapy. Methods We assessed the role of NFKBIA with various approaches, including in silico analyses, RNA-silencing and xenotransplantation. Western blot analyses, immunohistochemistry and RT-qPCR were used to detect the expression of specific proteins and genes. Immunoprecipitation and pull-down experiments were used to evaluate protein-protein interactions. Results Here, by using an in silico approach, following the identification of NFKBIA (the gene encoding IκBα) amplification in various cancers, we described an inverse correlation between IκBα, oxidative metabolism, and ROS production in lung cancer. Furthermore, we showed that novel IκBα targeting compounds combined with cisplatin treatment promote an increase in ROS beyond the tolerated threshold, thus causing death by oxytosis. Conclusions NFKBIA amplification and IκBα overexpression identify a unique cancer subtype associated with specific expression profile and metabolic signatures. Through p65-NFKB regulation, IκBα overexpression favors metabolic rewiring of cancer cells and distinct susceptibility to cisplatin. Lastly, we have developed a novel approach to disrupt IκBα/p65 interaction, restoring p65-mediated apoptotic responses to cisplatin due to mitochondria deregulation and ROS-production.

scholarly journals Linking metabolic dysfunction with cardiovascular diseases: Brn-3b/POU4F2 transcription factor in cardiometabolic tissues in health and disease

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Vishwanie S. Budhram-Mahadeo ◽  
Matthew R. Solomons ◽  
Eeshan A. O. Mahadeo-Heads
Keyword(s):  
Transcription Factor ◽  
Cardiovascular Diseases ◽  
Cell Fate ◽  
Target Genes ◽  
Cardiovascular Responses ◽  
Normal Function ◽  
Valuable Insight ◽  
Metabolic Dysfunction ◽  
Pathological Changes ◽  
Cardiac Responses

AbstractMetabolic and cardiovascular diseases are highly prevalent and chronic conditions that are closely linked by complex molecular and pathological changes. Such adverse effects often arise from changes in the expression of genes that control essential cellular functions, but the factors that drive such effects are not fully understood. Since tissue-specific transcription factors control the expression of multiple genes, which affect cell fate under different conditions, then identifying such regulators can provide valuable insight into the molecular basis of such diseases. This review explores emerging evidence that supports novel and important roles for the POU4F2/Brn-3b transcription factor (TF) in controlling cellular genes that regulate cardiometabolic function. Brn-3b is expressed in insulin-responsive metabolic tissues (e.g. skeletal muscle and adipose tissue) and is important for normal function because constitutive Brn-3b-knockout (KO) mice develop profound metabolic dysfunction (hyperglycaemia; insulin resistance). Brn-3b is highly expressed in the developing hearts, with lower levels in adult hearts. However, Brn-3b is re-expressed in adult cardiomyocytes following haemodynamic stress or injury and is necessary for adaptive cardiac responses, particularly in male hearts, because male Brn-3b KO mice develop adverse remodelling and reduced cardiac function. As a TF, Brn-3b regulates the expression of multiple target genes, including GLUT4, GSK3β, sonic hedgehog (SHH), cyclin D1 and CDK4, which have known functions in controlling metabolic processes but also participate in cardiac responses to stress or injury. Therefore, loss of Brn-3b and the resultant alterations in the expression of such genes could potentially provide the link between metabolic dysfunctions with adverse cardiovascular responses, which is seen in Brn-3b KO mutants. Since the loss of Brn-3b is associated with obesity, type II diabetes (T2DM) and altered cardiac responses to stress, this regulator may provide a new and important link for understanding how pathological changes arise in such endemic diseases.

scholarly journals Histone Acetyltransferases and Stem Cell Identity

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2407
Author(s):  
Ruicen He ◽  
Arthur Dantas ◽  
Karl Riabowol
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Histone Acetyltransferases ◽  
Specific Cell ◽  
Cell Fates ◽  
Cell Identity ◽  
Hematopoietic Stem

Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer stem cells.

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