Cell proliferation control by Notch signaling in Drosophila development

Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 2031-2040 ◽  
Author(s):  
M.J. Go ◽  
D.S. Eastman ◽  
S. Artavanis-Tsakonas
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Imaginal Disc ◽  
Synergistic Effects ◽  
Wing Disc ◽  
Notch Receptor ◽  
Simple Consequence ◽  
Undifferentiated Cells ◽  
Cell Proliferation Control ◽  
Stimulation Of

The Notch receptor mediates cell interactions controlling the developmental fate of a broad spectrum of undifferentiated cells. By modulating Notch signaling in specific precursor cells during Drosophila imaginal disc development, we demonstrate that Notch activity can influence cell proliferation. The activation of the Notch receptor in the wing disc induces the expression of the wing margin patterning genes vestigial and wingless, and strong mitotic activity. However, the effect of Notch signaling on cell proliferation is not the simple consequence of the upregulation of either vestigial or wingless. Vestigial and Wingless, on the contrary, display synergistic effects with Notch signaling, resulting in the stimulation of cell proliferation in imaginal discs.

scholarly journals Glutamate signaling at cytoneme synapses

2018 ◽  
Author(s):  
Hai Huang ◽  
Songmei Liu ◽  
Thomas B. Kornberg
Keyword(s):  
Imaginal Disc ◽  
Glutamate Transporter ◽  
Wing Disc ◽  
Calcium Transients ◽  
Glutamatergic Synapses ◽  
Glutamate Signaling ◽  
Epithelial Tube ◽  
Disc Cells ◽  
Synaptotagmin 1 ◽  
Stimulation Of

AbstractWe investigated the roles of neuronal synapse components for development of the Drosophila air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp from the wing imaginal disc. Dpp signaling in the ASP requires that disc cells express Dpp, Synaptobrevin, Synaptotagmin-1, the glutamate transporter, and a voltage-gated calcium channel, and that ASP cells express the Dpp receptor, Synaptotagmin-4 and the AMPA-type glutamate receptor GluRII. Calcium transients in ASP cytonemes correlate with signaling activity. Calcium transients in the ASP require GluRII, are activated by L-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and NASPM. Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic.SummaryParacrine signals transfer between Drosophila epithelial cells at glutamatergic synapses.

scholarly journals Glutamate signaling at cytoneme synapses

Science ◽  
2019 ◽  
Vol 363 (6430) ◽  
pp. 948-955 ◽  
Author(s):  
Hai Huang ◽  
Songmei Liu ◽  
Thomas B. Kornberg
Keyword(s):  
Imaginal Disc ◽  
Glutamate Transporter ◽  
Wing Disc ◽  
Glutamate Signaling ◽  
Neuronal Synapses ◽  
Morphogenetic Protein ◽  
Epithelial Tube ◽  
Disc Cells ◽  
Synaptotagmin 1 ◽  
Stimulation Of

We investigated the roles of components of neuronal synapses for development of the Drosophila air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp (Decapentaplegic, a homolog of the vertebrate bone morphogenetic protein) from the wing imaginal disc. Dpp signaling in the ASP was compromised if disc cells lacked Synaptobrevin and Synaptotagmin-1 (which function in vesicle transport at neuronal synapses), the glutamate transporter, and a voltage-gated calcium channel, or if ASP cells lacked Synaptotagmin-4 or the glutamate receptor GluRII. Transient elevations of intracellular calcium in ASP cytonemes correlate with signaling activity. Calcium transients in ASP cells depend on GluRII, are activated by l-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and by the GluR inhibitor NASPM (1-naphthylacetyl spermine trihydrochloride). Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic.

scholarly journals The Drosophila Importin-α3 Is Required for Nuclear Import of Notch In Vivo and It Displays Synergistic Effects with Notch Receptor on Cell Proliferation

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68247 ◽  
Author(s):  
Nalani Sachan ◽  
Abhinava K. Mishra ◽  
Mousumi Mutsuddi ◽  
Ashim Mukherjee
Keyword(s):  
Cell Proliferation ◽  
Nuclear Import ◽  
Synergistic Effects ◽  
Notch Receptor

scholarly journals Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta-Notch signaling to the air sac primordium

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Hai Huang ◽  
Thomas B Kornberg
Keyword(s):  
Notch Signaling ◽  
Imaginal Disc ◽  
Flight Muscle ◽  
Wing Disc ◽  
Wing Imaginal Disc ◽  
Relay System ◽  
Signal Relay ◽  
Disc Cells ◽  
Flight Muscles ◽  
Notch Activation

The flight muscles, dorsal air sacs, wing blades, and thoracic cuticle of the Drosophila adult function in concert, and their progenitor cells develop together in the wing imaginal disc. The wing disc orchestrates dorsal air sac development by producing decapentaplegic and fibroblast growth factor that travel via specific cytonemes in order to signal to the air sac primordium (ASP). Here, we report that cytonemes also link flight muscle progenitors (myoblasts) to disc cells and to the ASP, enabling myoblasts to relay signaling between the disc and the ASP. Frizzled (Fz)-containing myoblast cytonemes take up Wingless (Wg) from the disc, and Delta (Dl)-containing myoblast cytonemes contribute to Notch activation in the ASP. Wg signaling negatively regulates Dl expression in the myoblasts. These results reveal an essential role for cytonemes in Wg and Notch signaling and for a signal relay system in the myoblasts.

scholarly journals Notch signaling directly controls cell proliferation in the Drosophila wing disc

2000 ◽  
Vol 97 (6) ◽  
pp. 2609-2614 ◽  
Author(s):  
A. Baonza ◽  
A. Garcia-Bellido
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Wing Disc ◽  
Drosophila Wing

scholarly journals Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 521
Author(s):  
Catia Giovannini ◽  
Francesca Fornari ◽  
Fabio Piscaglia ◽  
Laura Gramantieri
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Hepatitis Virus ◽  
Notch Pathway ◽  
Notch Receptor ◽  
Gamma Secretase ◽  
Stem Cell Maintenance ◽  
Pathway Activation ◽  
Promising Therapeutic Approach ◽  
Conserved Genes

The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Therefore, while interfering with Notch signaling might represent a promising therapeutic approach, the complexity of Notch/ligands interactions and the variable consequences of their modulations raises concerns when performed in undefined molecular background. The gamma-secretase inhibitors (GSIs), representing the most utilized approach for Notch inhibition in clinical trials, are characterized by important adverse effects due to the non-specific nature of GSIs themselves and to the lack of molecular criteria guiding patient selection. In this review, we briefly summarize the mechanisms involved in Notch pathway activation in HCC supporting the development of alternatives to the γ-secretase pan-inhibitor for HCC therapy.

scholarly journals Current Views on the Roles of O-Glycosylation in Controlling Notch-Ligand Interactions

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 309
Author(s):  
Wataru Saiki ◽  
Chenyu Ma ◽  
Tetsuya Okajima ◽  
Hideyuki Takeuchi
Keyword(s):  
Notch Signaling ◽  
100Th Anniversary ◽  
Notch Receptor ◽  
Notch Receptors ◽  
Evolutionarily Conserved ◽  
Future Challenges ◽  
Ligand Interactions ◽  
Epidermal Growth ◽  
Notch Activation ◽  
Human Specific

The 100th anniversary of Notch discovery in Drosophila has recently passed. The Notch is evolutionarily conserved from Drosophila to humans. The discovery of human-specific Notch genes has led to a better understanding of Notch signaling in development and diseases and will continue to stimulate further research in the future. Notch receptors are responsible for cell-to-cell signaling. They are activated by cell-surface ligands located on adjacent cells. Notch activation plays an important role in determining the fate of cells, and dysregulation of Notch signaling results in numerous human diseases. Notch receptors are primarily activated by ligand binding. Many studies in various fields including genetics, developmental biology, biochemistry, and structural biology conducted over the past two decades have revealed that the activation of the Notch receptor is regulated by unique glycan modifications. Such modifications include O-fucose, O-glucose, and O-N-acetylglucosamine (GlcNAc) on epidermal growth factor-like (EGF) repeats located consecutively in the extracellular domain of Notch receptors. Being fine-tuned by glycans is an important property of Notch receptors. In this review article, we summarize the latest findings on the regulation of Notch activation by glycosylation and discuss future challenges.

scholarly journals Combined Application of Pan-AKT Inhibitor MK-2206 and BCL-2 Antagonist Venetoclax in B-Cell Precursor Acute Lymphoblastic Leukemia

2021 ◽  
Vol 22 (5) ◽  
pp. 2771
Author(s):  
Anna Richter ◽  
Elisabeth Fischer ◽  
Clemens Holz ◽  
Julia Schulze ◽  
Sandra Lange ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Morphological Changes ◽  
Synergistic Effects ◽  
Lymphoblastic Leukemia ◽  
Tumor Cell Proliferation ◽  
Akt Inhibitor ◽  
Akt Phosphorylation ◽  
Combined Application

Aberrant PI3K/AKT signaling is a hallmark of acute B-lymphoblastic leukemia (B-ALL) resulting in increased tumor cell proliferation and apoptosis deficiency. While previous AKT inhibitors struggled with selectivity, MK-2206 promises meticulous pan-AKT targeting with proven anti-tumor activity. We herein, characterize the effect of MK-2206 on B-ALL cell lines and primary samples and investigate potential synergistic effects with BCL-2 inhibitor venetoclax to overcome limitations in apoptosis induction. MK-2206 incubation reduced AKT phosphorylation and influenced downstream signaling activity. Interestingly, after MK-2206 mono application tumor cell proliferation and metabolic activity were diminished significantly independently of basal AKT phosphorylation. Morphological changes but no induction of apoptosis was detected in the observed cell lines. In contrast, primary samples cultivated in a protective microenvironment showed a decrease in vital cells. Combined MK-2206 and venetoclax incubation resulted in partially synergistic anti-proliferative effects independently of application sequence in SEM and RS4;11 cell lines. Venetoclax-mediated apoptosis was not intensified by addition of MK-2206. Functional assessment of BCL-2 inhibition via Bax translocation assay revealed slightly increased pro-apoptotic signaling after combined MK-2206 and venetoclax incubation. In summary, we demonstrate that the pan-AKT inhibitor MK-2206 potently blocks B-ALL cell proliferation and for the first time characterize the synergistic effect of combined MK-2206 and venetoclax treatment in B-ALL.

scholarly journals P62.09 PLGF Regulates Stimulation of Cell Proliferation and Glycolysis of Lung Adenocarcinoma Through Wnt/β-catenin Pathway

2021 ◽  
Vol 16 (3) ◽  
pp. S550-S551
Author(s):  
B. Han ◽  
W. Zhang ◽  
Y. Zhang ◽  
F. Qian ◽  
W. Zhou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Stimulation Of
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