scholarly journals The bHLH factors Dpn and members of the E(spl) complex mediate the function of Notch signalling regulating cell proliferation during wing disc development

Biology Open ◽  
2012 ◽  
Vol 1 (7) ◽  
pp. 667-676 ◽  
Author(s):  
B. P. San Juan ◽  
I. Andrade-Zapata ◽  
A. Baonza
Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2383-2393 ◽  
Author(s):  
A. Baonza ◽  
J.F. de Celis ◽  
A. Garcia-Bellido

The function of extramacrochaetae is required during the development of the Drosophila wing in processes such as cell proliferation and vein differentiation. extramacrochaetae encodes a transcription factor of the HLH family, but unlike other members of this family, Extramacrochaetae lacks the basic region that is involved in interaction with DNA. Some phenotypes caused by extramacrochaetae in the wing are similar to those observed when Notch signalling is compromised. Furthermore, maximal levels of extramacrochaetae expression in the wing disc are restricted to places where Notch activity is higher, suggesting that extramacrochaetae could mediate some aspects of Notch signalling during wing development. We have studied the relationships between extramacrochaetae and Notch in wing development, with emphasis on the processes of vein formation and cell proliferation. We observe strong genetic interaction between extramacrochaetae and different components of the Notch signalling pathway, suggesting a functional relationship between them. We show that the higher level of extramacrochaetae expression coincides with the domain of expression of Notch and its downstream gene Enhancer of split-m(beta). The expression of extramacrochaetae at the dorso/ventral boundary and in boundary cells between veins and interveins depends on Notch activity. We propose that at least during vein differentiation and wing margin formation, extramacrochaetae is regulated by Notch and collaborates with other Notch-downstream genes such as Enhancer of split-m(beta).


Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 2031-2040 ◽  
Author(s):  
M.J. Go ◽  
D.S. Eastman ◽  
S. Artavanis-Tsakonas

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.


2016 ◽  
Vol 28 (12) ◽  
pp. 1873 ◽  
Author(s):  
Xiao-Feng Sun ◽  
Xing-Hong Sun ◽  
Shun-Feng Cheng ◽  
Jun-Jie Wang ◽  
Yan-Ni Feng ◽  
...  

The Notch and transforming growth factor (TGF)-β signalling pathways play an important role in granulosa cell proliferation. However, the mechanisms underlying the cross-talk between these two signalling pathways are unknown. Herein we demonstrated a functional synergism between Notch and TGF-β signalling in the regulation of preantral granulosa cell (PAGC) proliferation. Activation of TGF-β signalling increased hairy/enhancer-of-split related with YRPW motif 2 gene (Hey2) expression (one of the target genes of the Notch pathway) in PAGCs, and suppression of TGF-β signalling by Smad3 knockdown reduced Hey2 expression. Inhibition of the proliferation of PAGCs by N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester (DAPT), an inhibitor of Notch signalling, was rescued by both the addition of ActA and overexpression of Smad3, indicating an interaction between the TGF-β and Notch signalling pathways. Co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) assays were performed to identify the point of interaction between the two signalling pathways. CoIP showed direct protein–protein interaction between Smad3 and Notch2 intracellular domain (NICD2), whereas ChIP showed that Smad3 could be recruited to the promoter regions of Notch target genes as a transcription factor. Therefore, the findings of the present study support the idea that nuclear Smad3 protein can integrate with NICD2 to form a complex that acts as a transcription factor to bind specific DNA motifs in Notch target genes, such as Hey1 and Hey2, and thus participates in the transcriptional regulation of Notch target genes, as well as regulation of the proliferation of PAGCs.


Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4261-4269 ◽  
Author(s):  
Michèle Crozatier ◽  
Bruno Glise ◽  
Alain Vincent

Hedgehog (Hh) signalling from posterior (P) to anterior (A) cells is the primary determinant of AP polarity in the limb field in insects and vertebrates. Hh acts in part by inducing expression of Decapentaplegic (Dpp), but how Hh and Dpp together pattern the central region of the Drosophila wing remains largely unknown. We have re-examined the role played by Collier (Col), a dose-dependent Hh target activated in cells along the AP boundary, the AP organiser in the imaginal wing disc. We found that col mutant wings are smaller than wild type and lack L4 vein, in addition to missing the L3-L4 intervein and mis-positioning of the anterior L3 vein. We link these phenotypes to col requirement for the local upregulation of both emc and N, two genes involved in the control of cell proliferation, the EGFR ligand Vein and the intervein determination gene blistered. We further show that attenuation of Dpp signalling in the AP organiser is also col dependent and, in conjunction with Vein upregulation, required for formation of L4 vein. A model recapitulating the molecular interplay between the Hh, Dpp and EGF signalling pathways in the wing AP organiser is presented.


Author(s):  
Wen Luo ◽  
Irene Garcia-Gonzalez ◽  
Macarena Fernandez-Chacon ◽  
Veronica Casquero-Garcia ◽  
Rui Benedito

AbstractArteries are thought to be formed by the induction of a highly conserved arterial genetic program in a subset of vessels experiencing an increase in pulsatile and oxygenated blood flow. Both VEGF and Notch signalling have been shown to be essential for the initial steps of arterial specification. Here, we combined inducible genetic mosaics and transcriptomics to modulate and understand the function of these signalling pathways on cell proliferation, arterial-venous differentiation and mobilization. We observed that endothelial cells with high VEGF or Notch signalling are not genetically pre-determined and can form both arteries and veins. Importantly, cells completely lacking the Notch-Rbpj transcriptional activator complex can form arteries when the Myc-dependent metabolic and cell-cycle activity is suppressed. Thus, arterial development does not require the induction of a Notch-dependent arterial differentiation program, but rather the timely suppression of the endothelial metabolism and cell-cycle, a process preceding arterial mobilization and complete differentiation.


Genome ◽  
1989 ◽  
Vol 31 (2) ◽  
pp. 612-619 ◽  
Author(s):  
J. Díaz-Benjumea ◽  
M. A. F. González Gaitán ◽  
A. García-Bellido

The developmental study of the wing disc in Drosophila has revealed the progressive appearance of heterogeneities in the anlage formation i.e., of symmetric compartments, of lineage restrictions for vein and intervein regions within compartments, and in mitotic waves. The genetic analysis of alleles in 28 loci that affect vein formation allows us to classify them, according to their phenotypic effects in mutant combinations, in several groups of synergism. These effects include changes in vein differentiation, vein pattern, and growth of the wing anlage. Clonal analyses of mutations of these groups shows that pattern differentiation is associated with changes in cell proliferation dynamics. The study of combinations of mutations from different groups allows us to infer the existence of distinct genetic operations in wing development. A model is presented relating these genetic operations to cell proliferation and cell communication in wing morphogenesis and vein patterning.Key words: pattern formation, morphogenesis, cell proliferation and differentiation.


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