Notch signalling and the initiation of neural development in the Drosophila eye

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 3889-3898 ◽  
Author(s):  
Antonio Baonza ◽  
Matthew Freeman
Keyword(s):  
Neural Development ◽  
Notch Signalling ◽  
The Other ◽  
Signalling Pathways ◽  
Notch Signalling Pathway ◽  
Drosophila Eye ◽  
Dependent Signal ◽  
Notch Activation ◽  
Number Of Cells

Neural determination in the Drosophila eye occurs progressively. A diffusible signal, Dpp, causes undetermined cells first to adopt a ‘pre-proneural’ state in which they are primed to start differentiating. A second signal is required to trigger the activation of the transcription factor Atonal, which causes the cells to initiate overt photoreceptor neurone differentiation. Both Dpp and the second signal are dependent on Hedgehog (Hh) signalling. Previous work has shown that the Notch signalling pathway also has a proneural role in the eye (as well as a later, opposite function when it restricts the number of cells becoming photoreceptors – a process of lateral inhibition). It is not clear how the early proneural role of Notch integrates with the other signalling pathways involved. We provide evidence that Notch activation by its ligand Delta is the second Hh-dependent signal required for neural determination. Notch activity normally only triggers Atonal expression in cells that have adopted the pre-proneural state induced by Dpp. We also report that Notch drives the transition from pre-proneural to proneural by downregulating two repressors of Atonal: Hairy and Extramacrochaetae.

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.

Notch signalling acts in postmitotic avian myogenic cells to control MyoD activation

Development ◽  
2001 ◽  
Vol 128 (1) ◽  
pp. 107-116 ◽  
Author(s):  
E. Hirsinger ◽  
P. Malapert ◽  
J. Dubrulle ◽  
M.C. Delfini ◽  
D. Duprez ◽  
...  
Keyword(s):  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Detailed Examination ◽  
Notch Signalling ◽  
Myogenic Cells ◽  
Myogenic Markers ◽  
Notch Activation

During Drosophila myogenesis, Notch signalling acts at multiple steps of the muscle differentiation process. In vertebrates, Notch activation has been shown to block MyoD activation and muscle differentiation in vitro, suggesting that this pathway may act to maintain the cells in an undifferentiated proliferative state. In this paper, we address the role of Notch signalling in vivo during chick myogenesis. We first demonstrate that the Notch1 receptor is expressed in postmitotic cells of the myotome and that the Notch ligands Delta1 and Serrate2 are detected in subsets of differentiating myogenic cells and are thus in position to signal to Notch1 during myogenic differentiation. We also reinvestigate the expression of MyoD and Myf5 during avian myogenesis, and observe that Myf5 is expressed earlier than MyoD, consistent with previous results in the mouse. We then show that forced expression of the Notch ligand, Delta1, during early myogenesis, using a retroviral system, has no effect on the expression of the early myogenic markers Pax3 and Myf5, but causes strong down-regulation of MyoD in infected somites. Although Delta1 overexpression results in the complete lack of differentiated muscles, detailed examination of the infected embryos shows that initial formation of a myotome is not prevented, indicating that exit from the cell cycle has not been blocked. These results suggest that Notch signalling acts in postmitotic myogenic cells to control a critical step of muscle differentiation.

A subset of notch functions during Drosophila eye development require Su(H) and the E(spl) gene complex

Development ◽  
1998 ◽  
Vol 125 (15) ◽  
pp. 2893-2900 ◽  
Author(s):  
P. Ligoxygakis ◽  
S.Y. Yu ◽  
C. Delidakis ◽  
N.E. Baker
Keyword(s):  
Cell Fate ◽  
Notch Pathway ◽  
Signal Transduction Pathway ◽  
Notch Signalling ◽  
Transduction Pathway ◽  
Notch Signalling Pathway ◽  
Bhlh Genes ◽  
Drosophila Eye ◽  
Enhancer Of Split ◽  
Signalling Process

The Notch signalling pathway is involved in many processes where cell fate is decided. Previous work showed that Notch is required at successive steps during R8 specification in the Drosophila eye. Initially, Notch enhances atonal expression and promotes atonal function. After atonal autoregulation has been established, Notch signalling represses atonal expression during lateral specification. In this paper we investigate which known components of the Notch pathway are involved in each signalling process. Using clonal analysis we show that a ligand of Notch, Delta, is required along with Notch for both proneural enhancement and lateral specification, while the downstream components Suppressor-of-Hairless and Enhancer-of-Split are involved only in lateral specification. Our data point to a distinct signal transduction pathway during proneural enhancement by Notch. Using misexpression experiments we also show that particular Enhancer-of-split bHLH genes can differ greatly in their contribution to lateral specification.

scholarly journals Notch signalling in ischaemia-induced angiogenesis

2009 ◽  
Vol 37 (6) ◽  
pp. 1221-1227 ◽  
Author(s):  
Ayman Al Haj Zen ◽  
Paolo Madeddu
Keyword(s):  
Notch Pathway ◽  
Therapeutic Angiogenesis ◽  
Notch Signalling ◽  
Signalling Pathways ◽  
Sprouting Angiogenesis ◽  
Vessel Maturation ◽  
Reparative Process ◽  
Novel Targets

Notch signalling represents a key pathway essential for normal vascular development. Recently, great attention has been focused on the implication of Notch pathway components in postnatal angiogenesis and regenerative medicine. This paper critically reviews the most recent findings supporting the role of Notch in ischaemia-induced neovascularization. Notch signalling reportedly regulates several steps of the reparative process occurring in ischaemic tissues, including sprouting angiogenesis, vessel maturation, interaction of vascular cells with recruited leucocytes and skeletal myocyte regeneration. Further characterization of Notch interaction with other signalling pathways might help identify novel targets for therapeutic angiogenesis.

Regulation of primordial follicle recruitment by cross-talk between the Notch and phosphatase and tensin homologue (PTEN)/AKT pathways

2016 ◽  
Vol 28 (6) ◽  
pp. 700 ◽  
Author(s):  
Lin-Qing Wang ◽  
Jing-Cai Liu ◽  
Chun-Lei Chen ◽  
Shun-Feng Cheng ◽  
Xiao-Feng Sun ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Butyl Ester ◽  
Primordial Follicle ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Negative Regulator ◽  
Signalling Pathways ◽  
Notch Signalling Pathway ◽  
Primordial Follicles ◽  
Phosphatase And Tensin Homologue

The growth of oocytes and the development of follicles require certain pathways involved in cell proliferation and survival, such as the phosphatidylinositol 3-kinase (PI3K) pathway and the Notch signalling pathway. The aim of the present study was to investigate the interaction between Notch and the PI3K/AKT signalling pathways and their effects on primordial follicle recruitment. When the Notch pathway was inhibited by L-685,458 or N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester (DAPT) in vitro, the expression of genes in the pathway and the percentage of oocytes in growing follicles decreased significantly in mouse ovaries. By 2 days postpartum, ovaries exposed to DAPT, short interference (si) RNA against Notch1 or siRNA against Hairy and enhancer of split-1 (Hes1) had significantly decreased expression of HES1, the target protein of the Notch signalling pathway. In contrast, expression of phosphatase and tensin homologue (Pten), a negative regulator of the AKT signalling pathway, was increased significantly. Co immunoprecipitation (Co-IP) revealed an interaction between HES1 and PTEN. In addition, inhibition of the Notch signalling pathway suppressed AKT phosphorylation and the proliferation of granulosa cells. In conclusion, the recruitment of primordial follicles was affected by the proliferation of granulosa cells and regulation of the interaction between the Notch and PI3K/AKT signalling pathways.

The role of presenilin 1 during somite segmentation

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1391-1402 ◽  
Author(s):  
K.i. Koizumi ◽  
M. Nakajima ◽  
S. Yuasa ◽  
Y. Saga ◽  
T. Sakai ◽  
...  
Keyword(s):  
Notch Pathway ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Paraxial Mesoderm ◽  
Presenilin 1 ◽  
Wild Type ◽  
Presomitic Mesoderm ◽  
Notch Signalling Pathway ◽  
Deficient Mice

The Notch signalling pathway plays essential roles during the specification of the rostral and caudal somite halves and subsequent segmentation of the paraxial mesoderm. We have re-investigated the role of presenilin 1 (Ps1; encoded by Psen1) during segmentation using newly generated alleles of the Psen1 mutation. In Psen1-deficient mice, proteolytic activation of Notch1 was significantly affected and the expression of several genes involved in the Notch signalling pathway was altered, including Δ-like3, Hes5, lunatic fringe (Lfng) and Mesp2. Thus, Ps1-dependent activation of the Notch pathway is essential for caudal half somite development. We observed defects in Notch signalling in both the caudal and rostral region of the presomitic mesoderm. In the caudal presomitic mesoderm, Ps1 was involved in maintaining the amplitude of cyclic activation of the Notch pathway, as represented by significant reduction of Lfng expression in Psen1-deficient mice. In the rostral presomitic mesoderm, rapid downregulation of the Mesp2 expression in the presumptive caudal half somite depends on Ps1 and is a prerequisite for caudal somite half specification. Chimaera analysis between Psen1-deficient and wild-type cells revealed that condensation of the wild-type cells in the caudal half somite was concordant with the formation of segment boundaries, while mutant and wild-type cells intermingled in the presomitic mesoderm. This implies that periodic activation of the Notch pathway in the presomitic mesoderm is still latent to segregate the presumptive rostral and caudal somite. A transient episode of Mesp2 expression might be needed for Notch activation by Ps1 to confer rostral or caudal properties. In summary, we propose that Ps1 is involved in the functional manifestation of the segmentation clock in the presomitic mesoderm.

Role of the Notch signalling pathway in tooth morphogenesis

2005 ◽  
Vol 50 (2) ◽  
pp. 137-140 ◽  
Author(s):  
Thimios A. Mitsiadis ◽  
Laure Regaudiat ◽  
Thomas Gridley
Keyword(s):  
Notch Signalling ◽  
Signalling Pathway ◽  
Notch Signalling Pathway ◽  
Tooth Morphogenesis

Role of Notch signalling pathway in cancer and its association with DNA methylation

2013 ◽  
Vol 92 (3) ◽  
pp. 667-675 ◽  
Author(s):  
MADHURI G. S. AITHAL ◽  
NARAYANAPPA RAJESWARI
Keyword(s):  
Dna Methylation ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Notch Signalling Pathway
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