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Of the 20 or so signal transduction pathways that orchestrate cell-cell interactions in metazoans, seven are involved during development. One of these is the Notch signalling pathway which regulates cellular identity, proliferation, differentiation and apoptosis via the developmental processes of lateral inhibition and boundary induction. In light...
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Proinflammatory Th1 cells can produce large amounts of the immunosuppressive cytokine IL-10, thereby facilitating the self-limitation of inflammatory responses. Recently, we identified the Notch pathway as a main regulator of IL-10 production by Th1 cells. In this study, we show that plasmacytoid dendritic cells (pDCs), by means of their unique hig...
Delta-like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target for cancer therapy. However, the potential side effects of blocking this pathway remain uncertain. Here we show that chronic DLL4 blockade causes pathological activation of endothelial cells, disrupts normal organ homeostasis and induces vascular tumours, raising impo...
Squamous odontogenic tumor (SOT) is a rare benign odontogenic epithelial neoplasm. A slow-growing painless expansive swelling is the common presenting symptom. Histopathologically, SOT can be easily misdiagnosed as an acanthomatous ameloblastoma. Although Notch receptors and ligands have been shown to play a role in cell fate decisions in ameloblas...
Studies have shown that Notch is essential for the maintenance of a T cell Th2 phenotype in vivo. It has also been shown that Notch ligands have diverse functions during T cell activation. We chose to investigate the role of Notch ligands during the Th2 response.
We studied the relationship of two Notch ligands, delta-like 4 and jagged-1, to T cell...
The Notch pathway is involved in cell-cell signaling during development and adulthood from invertebrates to higher eukaryotes. Activation of the Notch receptor by its ligands relies upon a multi-step processing. The extracellular part of the receptor is removed by a metalloprotease of the ADAM family and the remaining fragment is cleaved within its...
Citations
... Plays a role in cellular proliferation and angiogenesis [61]. ...
Wound healing involves a series of cellular and molecular processes to heal injured tissue. Growth factors such as vascular endothelial growth factor (VEGF), and signalling pathways such as phosphatidylinositol 3-kinase, protein kinase B, and mammalian target of rapamycin (PI3K/AKT/mTOR) are essential in wound healing.
VEGF is linked to intracellular signalling pathways including PI3K/AKT/mTOR, which controls cell growth, metabolism, proliferation, apoptosis, and protein synthesis. During photobiomodulation (PBM), low-level light in the visible red and near-infrared (NIR) spectrum is employed to promote healing, and reduce pain, inflammation,
and oedema. Several studies demonstrate that PBM enhances cellular survival, proliferation, migration, and viability in vitro, however, the exact cellular and molecular mechanisms responsible for these benefits have not yet been identified. The aim of this review is to explore the effects of PBM on the PI3K/AKT/mTOR signalling pathway in wound healing.
... Notch signaling is conserved across the animal kingdom [6][7][8]. Notch signaling plays crucial roles in various developmental events, encompassing cell fate determination, cell cycle progression, cell death and stem cell homeostasis [1][2][3][4][5]. Therefore, it is not surprising that mutations of genes encoding Notch signaling components contribute to various human The signal sending cell is in blue and the signal receiving cell is in earthy yellow. ...
Notch signaling is an evolutionarily conserved pathway which functions between adjacent cells to establish their distinct identities. Despite operating in a simple mechanism, Notch signaling plays remarkably diverse roles in development to regulate cell fate determination, organ growth and tissue patterning. While initially discovered and characterized in the model insect Drosophila melanogaster, recent studies across various insect species have revealed the broad involvement of Notch signaling in shaping insect tissues. This review focuses on providing a comprehensive picture regarding the roles of the Notch pathway in insect development. The roles of Notch in the formation and patterning of the insect embryo, wing, leg, ovary and several specific structures, as well as in physiological responses, are summarized. These results are discussed within the developmental context, aiming to deepen our understanding of the diversified functions of the Notch signaling pathway in different insect species.
... The evolutionarily conserved elements of the Notch pathway are presented throughout the entire Animalia kingdom. Phylogenetic studies suggest that the fundamental molecules of the pathway, the NOTCH receptors and ligands, have played essential roles in animal evolution [74]. In humans, four independent NOTCH (1, 2, 3, 4) genes located on the 9q34.3, ...
Notch1 signalling plays a multifaceted role in tissue development and homeostasis. Currently, due to the pivotal role of Notch1 signalling, the relationship between NOTCH1 expression and the development of health disorders is being intensively studied. Nevertheless, Notch1 signalling is not only controlled at the transcriptional level but also by a variety of post-translational events. First is the ligand-dependent mechanical activation of NOTCH receptors and then the intracellular crosstalk with other signalling molecules—among those are long non-coding RNAs (lncRNAs). In this review, we provide a detailed overview of the specific role of lncRNAs in the modulation of Notch1 signalling, from expression to activity, and their connection with the development of health disorders, especially cancers.
... The Notch signaling pathway is a well-conserved signaling pathway (King et al., 2008;Gazave et al., 2009) that is composed of the DSL (Delta/Serrate/Lag2) ligands and Notch receptors (Kopan and Ilagan, 2009). From a biochemical point of view, upon the binding of the DSL ligands and Notch receptors, the intracellular domain of Notch receptors (NICD) is cleaved from the cell membrane and translocated in the nucleus to transduce the signal (Struhl and Adachi, 1998). ...
Notch signaling is necessary for the development of many organ systems, including the nervous system, biliary system, and visual and auditory sensory systems. This signaling pathway is composed of DSL ligands and Notch receptors. Upon the interaction of those components between neighboring cells, the intracellular domain of the Notch receptor is cleaved from the cell membrane to act as a transcription factor. To date, many mechanistic insights, including lateral inhibition and lateral induction, have been proposed from observation of patterning morphogenesis and expression profiles of Notch signaling-associated molecules. The lack of a direct measurement method for Notch signaling, however, has impeded the examination of those mechanistic insights. In this mini-review, recent advances in the direct measurement of Notch signaling are introduced with a focus on the application of genetic modification of Notch receptors with the components of the Cre/loxP system and Gal4/UAS system. The combination of such conventional genetic techniques is opening a new era in Notch signaling biology by direct visualization of Notch “signaling” in addition to Notch signaling-associated molecules.
... The first sponge genome sequenced, from the demosponge Amphimedon queenslandica, revealed a larger size and gene content than expected [18][19][20]. However, transcriptomic data from other species indicated that A. queenslandica was not representative of the diversity of sponges [17,[21][22][23][24][25][26]. Several sponge genomes now sequenced [27][28][29][30][31] illustrate the disparity of sponge genomes in terms of size, features of noncoding regions, and gene repertoire [3,28]. ...
Background
Explaining the emergence of the hallmarks of bilaterians is a central focus of evolutionary developmental biology—evodevo—and evolutionary genomics. For this purpose, we must both expand and also refine our knowledge of non-bilaterian genomes, especially by studying early branching animals, in particular those in the metazoan phylum Porifera.
Results
We present a comprehensive analysis of the first whole genome of a glass sponge, Oopsacas minuta, a member of the Hexactinellida. Studying this class of sponge is evolutionary relevant because it differs from the three other Porifera classes in terms of development, tissue organization, ecology, and physiology. Although O. minuta does not exhibit drastic body simplifications, its genome is among the smallest of animal genomes sequenced so far, and surprisingly lacks several metazoan core genes (including Wnt and several key transcription factors). Our study also provides the complete genome of a symbiotic Archaea dominating the associated microbial community: a new Thaumarchaeota species.
Conclusions
The genome of the glass sponge O. minuta differs from all other available sponge genomes by its compactness and smaller number of encoded proteins. The unexpected loss of numerous genes previously considered ancestral and pivotal for metazoan morphogenetic processes most likely reflects the peculiar syncytial tissue organization in this group. Our work further documents the importance of convergence during animal evolution, with multiple convergent evolution of septate-like junctions, electrical-signaling and multiciliated cells in metazoans.
... Molecules of the Notch pathway control the dental cell-type specificity and mediate their distinct responses to common signals [48]. On a broader scale, Notch signaling is the central hub of a molecular network that determines cell fate choice throughout animal development, homeostasis, and regeneration via lateral inhibition [8,18,[116][117][118][119]. A flat hierarchy of gene regulation [18,118] upon Notch signaling deletion could thus revert the evolutionary path, impairing the specialization of the cells that contribute to amelogenesis and thus generating structures resembling more enameloid of fishes than enamel of mammals [42]. ...
The Notch pathway is an ancient, evolutionary conserved intercellular signaling mechanism that is involved in cell fate specification and proper embryonic development. The Jagged2 gene, which encodes a ligand for the Notch family of receptors, is expressed from the earliest stages of odontogenesis in epithelial cells that will later generate the enamel-producing ameloblasts. Homozygous Jagged2 mutant mice exhibit abnormal tooth morphology and impaired enamel deposition. Enamel composition and structure in mammals are tightly linked to the enamel organ that represents an evolutionary unit formed by distinct dental epithelial cell types. The physical cooperativity between Notch ligands and receptors suggests that Jagged2 deletion could alter the expression profile of Notch receptors, thus modifying the whole Notch signaling cascade in cells within the enamel organ. Indeed, both Notch1 and Notch2 expression are severely disturbed in the enamel organ of Jagged2 mutant teeth. It appears that the deregulation of the Notch signaling cascade reverts the evolutionary path generating dental structures more reminiscent of the enameloid of fishes rather than of mammalian enamel. Loss of interactions between Notch and Jagged proteins may initiate the suppression of complementary dental epithelial cell fates acquired during evolution. We propose that the increased number of Notch homologues in metazoa enabled incipient sister cell types to form and maintain distinctive cell fates within organs and tissues along evolution.
... Notch signaling is evolutionarily conserved [18]. Notch signaling is a cascade response that plays a key role in developmental processes, homeostasis and cell differentiation [8]. ...
Background
Gastric cancer is a common cause of death from cancer and an important global health care issue. Consequently, there is an urgent need to find new drugs and therapeutic targets for the treatment of gastric cancer. Recent studies have shown that tocotrienols (T3) have significant anticancer ability in cancer cell lines. Our previous study found that γ-tocotrienol (γ-T3) induced apoptosis in gastric cancer cells. We further explored the possible mechanisms of γ-T3 therapy for gastric cancer.
Methods
In this study, we treated gastric cancer cells with γ-T3, collect and deposit the cells. γ-T3-treated gastric cancer cells group and untreated group were subjected to RNA-seq assay, and analysis of sequencing results.
Results
Consistent with our previous findings, the results suggest that γ-T3 can inhibit mitochondrial complexes and oxidative phosphorylation. Analysis reveals that γ-T3 has altered mRNA and ncRNA in gastric cancer cells. Significantly altered signaling pathways after γ-T3 treatment were enriched for human papillomavirus infection (HPV) pathway and notch signaling pathway. The same significantly down-regulated genes notch1 and notch2 were present in both pathways in γ-T3-treated gastric cancer cells compared to controls.
Conclusions
It is indicated that γ-T3 may cure gastric cancer by inhibiting the notch signaling pathway. To provide a new and powerful basis for the clinical treatment of gastric cancer.
... Many genes from essential pathways during larval development were annotated in M. coruscus, such as the Notch signaling pathway, apoptosis, dorsoventral axis formation, and axon regeneration. Notch signaling is considered an evolutionarily conserved cell interaction mechanism, which plays a fundamental role in determining cells' fate during the development of invertebrate and vertebrate species [59,60]. Notch signaling has a significant effect on proliferation, differentiation, and apoptotic programs, influencing organ formation and morphogenesis [61]. ...
Many marine invertebrate larvae undergo complex morphological and physiological changes during the planktonic—benthic transition (a.k.a. metamorphosis). In this study, transcriptome analysis of different developmental stages was used to uncover the molecular mechanisms underpinning larval settlement and metamorphosis of the mussel, Mytilus coruscus. Analysis of highly upregulated differentially expressed genes (DEGs) at the pediveliger stage revealed enrichment of immune-related genes. The results may indicate that larvae co-opt molecules of the immune system to sense and respond to external chemical cues and neuroendocrine signaling pathways forecast and trigger the response. The upregulation of adhesive protein genes linked to byssal thread secretion indicates the anchoring capacity required for larval settlement arises prior to metamorphosis. The results of gene expression support a role for the immune and neuroendocrine systems in mussel metamorphosis and provide the basis for future studies to disentangle gene networks and the biology of this important lifecycle transformation.
... The ubiquitous Notch pathway is an ancient, highly conserved signalling system whose early appearance in evolution coincided with the emergence of multicellularity [1,2]. It was the first cell receptor signal transduction pathway to be discovered, more than a century ago, and decades of research since then have established that it is a central regulator of cell fate [1,2] that underpins normal embryo development and tissue homeostasis, from controlling the fine-grain patterning of insect eyes and wings, to orchestrating vertebrate segmentation, neurogenesis, angiogenesis, and turnover and differentiation of the gastro-intestinal tract [3][4][5][6][7][8]. ...
... The ubiquitous Notch pathway is an ancient, highly conserved signalling system whose early appearance in evolution coincided with the emergence of multicellularity [1,2]. It was the first cell receptor signal transduction pathway to be discovered, more than a century ago, and decades of research since then have established that it is a central regulator of cell fate [1,2] that underpins normal embryo development and tissue homeostasis, from controlling the fine-grain patterning of insect eyes and wings, to orchestrating vertebrate segmentation, neurogenesis, angiogenesis, and turnover and differentiation of the gastro-intestinal tract [3][4][5][6][7][8]. Moreover, corruption of this network has been implicated in numerous pathologies including neurovascular diseases (CADASIL), multisystem disorders (ALAGILLE syndrome) [9] as well as the majority of solid tumours [10][11][12]. ...
All tissue development and replenishment relies upon the breaking of symmetries leading to the morphological and operational differentiation of progenitor cells into more specialized cells. One of the main engines driving this process is the Notch signal transduction pathway, a ubiquitous signalling system found in the vast majority of metazoan cell types characterized to date. Broadly speaking, Notch receptor activity is governed by a balance between two processes: 1) intercellular Notch transactivation triggered via interactions between receptors and ligands expressed in neighbouring cells; 2) intracellular cis inhibition caused by ligands binding to receptors within the same cell. Additionally, recent reports have also unveiled evidence of cis activation. Whilst context-dependent Notch receptor clustering has been hypothesized, to date, Notch signalling has been assumed to involve an interplay between receptor and ligand monomers. In this study, we demonstrate biochemically, through a mutational analysis of DLL4, both in vitro and in tissue culture cells, that Notch ligands can efficiently self-associate. We found that the membrane proximal EGF-like repeat of DLL4 was necessary and sufficient to promote oligomerization/dimerization. Mechanistically, our experimental evidence supports the view that DLL4 ligand dimerization is specifically required for cis-inhibition of Notch receptor activity. To further substantiate these findings, we have adapted and extended existing ordinary differential equation-based models of Notch signalling to take account of the ligand dimerization-dependent cis-inhibition reported here. Our new model faithfully recapitulates our experimental data and improves predictions based upon published data. Collectively, our work favours a model in which net output following Notch receptor/ligand binding results from ligand monomer-driven Notch receptor transactivation (and cis activation) counterposed by ligand dimer-mediated cis-inhibition.
... The NOTCH signaling pathway is known to be one among the significant paracrine signaling pathways that is responsible for playing several roles such as cell identity, proliferation, differentiation, and apoptosis in organisms [57]. Various studies have been carried out in the Drosophila in order to demonstrate the pathway it chooses for the means of signaling [58]. ...
DNA methylation is one among the major grounds of cancer progression which is characterized by the addition of a methyl group to the promoter region of the gene thereby causing gene silencing or increasing the probability of mutations; however, in bacteria, methylation is used as a defense mechanism where DNA protection is by addition of methyl groups making restriction enzymes unable to cleave. Hypermethylation and hypomethylation both pose as leading causes of oncogenesis; the former being more frequent which occurs at the CpG islands present in the promoter region of the genes, whereas the latter occurs globally in various genomic sequences. Reviewing methylation profiles would help in the detection and treatment of cancers. Demethylation is defined as preventing methyl group addition to the cytosine DNA base which could cause cancers in case of global hypomethylation, however, upon further investigation; it could be used as a therapeutic tool as well as for drug design in cancer treatment. In this review, we have studied the molecules that induce and enzymes (DNMTs) that bring about methylation as well as comprehend the correlation between methylation with transcription factors and various signaling pathways. DNA methylation has also been reviewed in terms of how it could serve as a prognostic marker and the various therapeutic drugs that have come into the market for reversing methylation opening an avenue toward curing cancers.
