scholarly journals DLK1 Protein Expression during Mouse Development Provides New Insights into Its Function

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
F. A. Falix ◽  
M. R. S. Tjon-A-Loi ◽  
I. C. Gaemers ◽  
D. C. Aronson ◽  
W. H. Lamers
Keyword(s):  
Central Nervous System ◽  
Protein Expression ◽  
Posttranscriptional Regulation ◽  
Expression Patterns ◽  
Branching Morphogenesis ◽  
Notch Signalling ◽  
Mouse Embryos ◽  
Mouse Development ◽  
Notch Signalling Pathway ◽  
Mild Phenotype

Delta-like 1 homolog (DLK1) is a noncanonical ligand in the Delta-Notch signalling pathway. Although Dlk1 mRNA is abundantly present embryonically and declines rapidly just before birth, Dlk1 knockouts display a relatively mild phenotype. To assess whether this mild phenotype was due to posttranscriptional regulation, we studied the expression of DLK1 protein in mouse embryos and found abundant expression in liver, lung, muscle, vertebrae, pancreas, pituitary, and adrenal gland(s). DLK1 expression was absent in heart, stomach, intestine, kidney, epidermis, and central nervous system. DLK1 protein expression, therefore, correlates well with the reported Dlk1 mRNA expression pattern, which shows that its expression is mainly regulated at the pretranslational level. The comparison of the reported expression patterns of Notch mRNA and those of DLK1 in organs where lineage commitment and branching morphogenesis are important developmental processes suggests that DLK1 is a ligand that prevents premature Notch-dependent differentiation, possibly by competing with canonical ligands.

Protein expression patterns of identified neurons and of sprouting cells from the leech central nervous system

2000 ◽  
Vol 44 (3) ◽  
pp. 320-332 ◽  
Author(s):  
Xueqing Wu ◽  
Barbara Ritter ◽  
Jan Henrik Schlattjan ◽  
Volkmar Lessmann ◽  
Rolf Heumann ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Expression ◽  
Expression Patterns ◽  
Identified Neurons

Feedback regulation is central to Delta-Notch signalling required for Drosophila wing vein morphogenesis

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3283-3291 ◽  
Author(s):  
S.S. Huppert ◽  
T.L. Jacobsen ◽  
M.A. Muskavitch
Keyword(s):  
Protein Expression ◽  
Cell Fate ◽  
Expression Patterns ◽  
Feedback Regulation ◽  
Notch Signalling ◽  
Notch Receptor ◽  
Cell Fates ◽  
Wing Vein ◽  
Drosophila Wing ◽  
Puparium Formation

Delta and Notch are required for partitioning of vein and intervein cell fates within the provein during Drosophila metamorphosis. We find that partitioning of these fates is dependent on Delta-mediated signalling from 22 to 30 hours after puparium formation at 25 degrees C. Within the provein, Delta is expressed more highly in central provein cells (presumptive vein cells) and Notch is expressed more highly in lateral provein cells (presumptive intervein cells). Accumulation of Notch in presumptive intervein cells is dependent on Delta signalling activity in presumptive vein cells and constitutive Notch receptor activity represses Delta accumulation in presumptive vein cells. When Delta protein expression is elevated ectopically in presumptive intervein cells, complementary Delta and Notch expression patterns in provein cells are reversed, and vein loss occurs because central provein cells are unable to stably adopt the vein cell fate. Our findings imply that Delta-Notch signalling exerts feedback regulation on Delta and Notch expression during metamorphic wing vein development, and that the resultant asymmetries in Delta and Notch expression underlie the proper specification of vein and intervein cell fates within the provein.

scholarly journals Frequency of polymorphisms and protein expression of cyclin-dependent kinase inhibitor 1A (CDKN1A) in central nervous system tumors

2009 ◽  
Vol 127 (5) ◽  
pp. 288-294 ◽  
Author(s):  
Mev Dominguez Valentin ◽  
Renata Canalle ◽  
Rosane de Paula Queiroz ◽  
Luiz Gonzaga Tone
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Expression ◽  
Kinase Inhibitor ◽  
Expression Patterns ◽  
Cns Tumors ◽  
Control Group ◽  
Cyclin Dependent Kinase ◽  
Cross Sectional ◽  
Cyclin Dependent Kinase Inhibitor

CONTEXT AND OBJECTIVE: Genetic investigation of central nervous system (CNS) tumors provides valuable information about the genes regulating proliferation, differentiation, angiogenesis, migration and apoptosis in the CNS. The aim of our study was to determine the prevalence of genetic polymorphisms (codon 31 and 3' untranslated region, 3'UTR) and protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene in patients with and without CNS tumors. DESIGN AND SETTING: Analytical cross-sectional study with a control group, at the Molecular Biology Laboratory, Pediatric Oncology Department, Hospital das Clínicas de Ribeirão Preto. METHODS: 41 patients with CNS tumors and a control group of 161 subjects without cancer and paires for sex, age and ethnicity were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Protein analysis was performed on 36 patients with CNS tumors, using the Western Blotting technique. RESULTS: The frequencies of the heterozygote (Ser/Arg) and polymorphic homozygote (Arg/Arg) genotypes of codon 31 in the control subjects were 28.0% and 1.2%, respectively. However, the 3'UTR site presented frequencies of 24.2% (C/T) and 0.6% (T/T). These frequencies were not statistically different (P > 0.05) from those seen in the patients with CNS tumors (19.4% and 0.0%, codon 31; 15.8% and 2.6%, 3'UTR site). Regarding the protein expression in ependymomas, 66.67% did not express the protein CDKN1A. The results for medulloblastomas and astrocytomas were similar: neither of them expressed the protein (57.14% and 61.54%, respectively). CONCLUSION: No significant differences in protein expression patterns or polymorphisms of CDKN1A in relation to the three types of CNS tumors were observed among Brazilian subjects.

scholarly journals The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo

Development ◽  
1994 ◽  
Vol 120 (12) ◽  
pp. 3537-3548 ◽  
Author(s):  
B. Jennings ◽  
A. Preiss ◽  
C. Delidakis ◽  
S. Bray
Keyword(s):  
Protein Expression ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Drosophila Embryo ◽  
Protein Accumulation ◽  
Notch Signalling Pathway ◽  
Cell Fate Decisions ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Enhancer Of Split

The Enhancer of split locus is required during many cell-fate decisions in Drosophila, including the segregation of neural precursors in the embryo. We have generated monoclonal antibodies that recognise some of the basic helix-loop-helix proteins encoded by the Enhancer of split locus and have used them to examine expression of Enhancer of split proteins during neurogenesis. The proteins are expressed in a dynamic pattern in the ventral neurogenic region and are confined to those ectodermal cells that surround a neuroblast in the process of delaminating. There is no staining in the neuroblasts themselves. We have also examined the relationship between Enhancer of split protein accumulation and the Notch signalling pathway. Protein expression is abolished in a number of neurogenic mutant backgrounds, including Notch, but is increased as a result of expressing a constitutively active Notch product. We conclude that Notch signalling activity is directly responsible for the accumulation of basic helix-loop-helix proteins encoded by the Enhancer of split locus.

Impact of Growth Factor Independence 1 in Human T-Cell Lymphomas; Pathogenic Potential Identified by Insertional Mutagenesis in a Murine T-Cell Lymphoma Model.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5047-5047
Author(s):  
Magdalena Julia Dabrowska ◽  
Karen Dybkaer ◽  
Preben Johansen ◽  
Hans Erik Johnsen ◽  
Finn Skou Pedersen
Keyword(s):  
T Cell ◽  
Protein Expression ◽  
Posttranscriptional Regulation ◽  
Immunohistochemical Staining ◽  
Insertional Mutagenesis ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Human T Cell

Abstract Abstract 5047 Introduction The transcriptional repressor and oncogene Growth factor independence 1 (Gfi1) has a major oncogenic potential and is aberrantly expressed in murine lymphomas and several human cancers. Gfi1 is a key regulator of stem cell quiescence and plays a significant role in T-cell development, lineage commitment, and influences development of maturate granulocytes and monocytes. The genomic locus on murine chromosome 5 encoding Gfi1 is a frequent integration locus activated in T-cell lymphomas induced by the SL3-3 Murine Leukemia Virus (MLV) as well as other MLVs, indicating that Gfi1 is essential in development of these tumors. In the SL3-3 induced T-cell lymphoma model, retroviral insertions in the Gfi1 3'UTR have been demonstrated to decouple microRNA-mediated posttranscriptional regulation of protein expression (Dabrowska et al, 2009) further supporting its role in lymphomagenesis. In human cancers, Gfi1 protein expression has been observed in HTLV-1 induced ATLL and SCLC but no knowledge exists on how Gfi1 contributes to initiating and maintaining human T-cell lymphomas. Methods Gfi1 gene and protein expression patterns were determined in precursor and mature human T-cell lymphomas by real time PCR and Western blot analysis. Furthermore, localization and expression patterns of the Gfi1 protein was determined in the human T-cell lymphomas by immunohistochemical staining with Gfi1 antibodies and compared to similar staining of MLV induced tumors. Results Our results demonstrated that Gfi1 mRNA and protein levels vary significantly among the human T-cell lymphomas, and do not always show a direct proportional pattern. Thus, Gfi1 mRNA expression can be relatively high without resulting in a corresponding high protein expression, suggesting that a microRNA mediated posttranscriptional regulation exists in some tumors but may be disrupted in others. Furthermore, an additional Gfi1 protein variant was identified in one of the T-cell lymphoma entities. Immunohistochemical staining demonstrated varying Gfi1 protein expression in both nucleus and cytoplasm in the T-cell lymphomas and different distributions of the protein within the tumor and tumor cells were observed among samples. Staining of normal human tonsil demonstrated Gfi1 protein to be localized in the cytoplasm. We hypothesise that regulation of Gfi1 may include shuttling between cytoplasm and nucleus and that lymphomagenesis enables unlimited nuclear access. Conclusion Our data shows that deregulated Gfi1 expression plays a major role in the development of MLV induced lymphomas and strongly indicates that retroviral insertional mutagenesis in murine models of human NHLs can be used to identify new genes involved in lymphomagenesis and, by use of functional assays, their impact on human lymphomas can be evaluated. Disclosures No relevant conflicts of interest to declare.

scholarly journals 236.Differential expression of monocarboxylate cotransporter proteins in preimplantation embryos

2004 ◽  
Vol 16 (9) ◽  
pp. 236 ◽  
Author(s):  
S. Jansen ◽  
M. Pantaleon ◽  
P. Kaye
Keyword(s):  
Expression Profiles ◽  
Expression Patterns ◽  
Cell Mass ◽  
Mouse Embryos ◽  
Preimplantation Development ◽  
Preimplantation Embryos ◽  
Confocal Laser ◽  
Cell Contact ◽  
Cleavage Stage ◽  
Mouse Development

During preimplantation development mouse embryos demonstrate a switch in substrate preference. Pyruvate consumption, high during the first few cleavage stages, declines as the morula develops to a blastocyst, when glucose becomes the preferred substrate. Whilst pyruvate utilisation has been well characterised, changes in the function and expression of pyruvate transporters during this crucial period remain unclear. Pyruvate, lactate and other monocarboxylates are transported across mammalian cell membranes via a specific H+-monocarboxylate cotransporter (MCT). Fourteen members of this family have been identified of which MCT1, MCT2 and MCT4 are well characterised. Although mRNA expression profiles are known during early mouse development (1,2), the specific roles of each protein isoform are unknown. In order to understand these, the expression pattern for each isoform and their cellular localisation during preimplantation development have been determined. Mouse embryos were freshly collected from superovulated Quackenbush mice at 24, 48, 72 and 96 h post-hCG and expression of MCT1, MCT2 and MCT4 analysed by confocal laser scanning immunohistochemistry. Our results confirm that all three MCT proteins are expressed in preimplantation embryos. Immunoreactivity for MCT1 and MCT2 appears diffuse throughout the cytoplasm of cleavage stage embryos. As development proceeds, MCT1 localised to the basolateral membranes of morulae and blastocysts, whilst stronger MCT2 expression was found on the apical trophectoderm as well as the inner cell mass. MCT4 immunoreactivity on the other hand is apparent at cell-cell contact sites in cleavage stage embryos and morulae, but it is not apparent in the blastocyst. The demonstration of different expression patterns for MCT1, MCT2 and MCT4 in mouse embryos implies specific functional roles for each in the critical regulation of H+, pyruvate and lactate transport during preimplantation development. (1) Harding EA, Day ML, Gibb CA, Johnson MH, Cook DI (1999) The activity of the H+-monocarboxylate cotransporter during pre-implantation development in the mouse. Eur. J. Physiol. 438, 397–404. (2) H�rubel F, El Mouatassim S, Gu�rin P, Frydman R, M�n�zo Y (2002) Genetic expression of monocarboxylate transporters during human and murine oocyte maturation and early embryonic development. Zygote 10, 175–181.

scholarly journals The role of Notch ligand, Delta-like ligand 4 (DLL4), in cancer angiogenesis—implications for therapy

2021 ◽  
Author(s):  
Marlena Brzozowa-Zasada
Keyword(s):  
Cancer Therapy ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Gamma Secretase ◽  
Tumour Angiogenesis ◽  
Notch Signalling Pathway ◽  
Expression Levels ◽  
Blocking Agents ◽  
Anti Cancer

Summary Background It is generally accepted that angiogenesis is a complex and tightly regulated process characterized by the growth of blood vessels from existing vasculature. Activation of the Notch signalling pathway affects multiple aspects of vascular development. One of the components of the Notch signalling pathway, Delta-like ligand 4 (DLL4), has recently appeared as a critical regulator of tumour angiogenesis and thus as a promising therapeutic target. Methods This review article includes available data from peer-reviewed publications associated with the role of DLL4 in cancer angiogenesis. Searches were performed in PubMed, EMBASE, Google Scholar and Web of Science using the terms “tumour angiogenesis”, “DLL4”, “Notch signalling” and “anti-cancer therapy”. Results The survival curves of cancer patients revealed that the patients with high DLL4 expression levels had significantly shorter survival times than the patients with low DLL4 expression. Moreover, a positive correlation was also identified between DLL4 and VEGF receptorsʼ expression levels. It seems that inhibition of DLL4 may exert potent growth inhibitory effects on some tumours resistant to anti-VEGF therapies. A great number of blocking agents of DLL4/Notch signalling including anti-DLL4 antibodies, DNA vaccination, Notch antibodies and gamma-secretase inhibitors have been studied in preclinical tumour models. Conclusion DLL4 seems to be a promising target in anti-cancer therapy. Nevertheless, the careful evaluation of adverse effects on normal physiological processes in relation to therapeutic doses of anti-DLL4 drugs will be significant for advancement of DLL4 blocking agents in clinical oncology.

scholarly journals Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zeyang Wang ◽  
Zhi Lv ◽  
Qian Xu ◽  
Liping Sun ◽  
Yuan Yuan
Keyword(s):  
Gastric Cancer ◽  
Functional Analysis ◽  
Protein Expression ◽  
Epstein Barr Virus ◽  
Protein Profile ◽  
Expression Patterns ◽  
Clinicopathological Parameters ◽  
Differential Proteomics ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background Epstein-Barr virus-associated gastric cancer (EBVaGC) is the most common EBV-related malignancy. A comprehensive research for the protein expression patterns in EBVaGC established by high-throughput assay remains lacking. In the present study, the protein profile in EBVaGC tissue was explored and related functional analysis was performed. Methods Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) was applied to EBV detection in GC cases. Data-independent acquisition (DIA) mass spectrometry (MS) was performed for proteomics assay of EBVaGC. Functional analysis of identified proteins was conducted with bioinformatics methods. Immunohistochemistry (IHC) staining was employed to detect protein expression in tissue. Results The proteomics study for EBVaGC was conducted with 7 pairs of GC cases. A total of 137 differentially expressed proteins in EBV-positive GC group were identified compared with EBV-negative GC group. A PPI network was constructed for all of them, and several proteins with relatively high interaction degrees could be the hub genes in EBVaGC. Gene enrichment analysis showed they might be involved in the biological pathways related to energy and biochemical metabolism. Combined with GEO datasets, a highly associated protein (GBP5) with EBVaGC was screened out and validated with IHC staining. Further analyses demonstrated that GBP5 protein might be associated with clinicopathological parameters and EBV infection in GC. Conclusions The newly identified proteins with significant differences and potential central roles could be applied as diagnostic markers of EBVaGC. Our study would provide research clues for EBVaGC pathogenesis as well as novel targets for the molecular-targeted therapy of EBVaGC.

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