Notch signalling mediates segmentation of the Drosophila leg

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4617-4626 ◽  
Author(s):  
J.F. de Celis ◽  
D.M. Tyler ◽  
J. de Celis ◽  
S.J. Bray
Keyword(s):  
Gene Expression ◽  
Imaginal Disc ◽  
Flexible Structures ◽  
Notch Signalling ◽  
Pupal Development ◽  
Suppressor Of Hairless ◽  
Leg Development ◽  
Somite Formation ◽  
Enhancer Of Split ◽  
Notch Activation

The legs of Drosophila are divided into segments along the proximodistal axis by flexible structures called joints. The separation between segments is already visible in the imaginal disc as folds of the epithelium, and cells at segment boundaries have different morphology during pupal development. We find that Notch is locally activated in distal cells of each segment, as demonstrated by the restricted expression of the Enhancer of split mbeta gene, and is required for the formation of normal joints. The genes fringe, Delta, Serrate and Suppressor of Hairless, also participate in Notch function during leg development, and their expression is localised within the leg segments with respect to segment boundaries. The failure to form joints when Notch signalling is compromised leads to shortened legs, suggesting that the correct specification of segment boundaries is critical for normal leg growth. The requirement for Notch during leg development resembles that seen during somite formation in vertebrates and at the dorsal ventral boundary of the wing, suggesting that the creation of boundaries of gene expression through Notch activation plays a conserved role in co-ordinating growth and patterning.

Composite signalling from Serrate and Delta establishes leg segments in Drosophila through Notch

Development ◽  
1999 ◽  
Vol 126 (13) ◽  
pp. 2993-3003 ◽  
Author(s):  
S.A. Bishop ◽  
T. Klein ◽  
A.M. Arias ◽  
J.P. Couso
Keyword(s):  
Gene Expression ◽  
Notch Signalling ◽  
Receptor Protein ◽  
General Mechanism ◽  
Developmental Processes ◽  
Downstream Gene Expression ◽  
Enhancer Of Split ◽  
Notch Activation

The receptor protein NOTCH and its ligands SERRATE and DELTA are involved in many developmental processes in invertebrates and vertebrates alike. Here we show that the expression of the Serrate and Delta genes patterns the segments of the leg in Drosophila by a combination of their signalling activities. Coincident stripes of Serrate and Delta expressing cells activate Enhancer of split expression in adjacent cells through Notch signalling. These cells form a patterning boundary from which a putative secondary signal leads to the development of leg joints. Elsewhere in the tarsal segments, signalling by DELTA and NOTCH is necessary for the development of non-joint parts of the leg. We propose that these two effects result from different thresholds of NOTCH activation, which are translated into different downstream gene expression effects. We propose a general mechanism for creation of boundaries by Notch signalling.

Functional relationships between Notch, Su(H) and the bHLH genes of the E(spl) complex: the E(spl) genes mediate only a subset of Notch activities during imaginal development

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2719-2728 ◽  
Author(s):  
J.F. de Celis ◽  
J. de Celis ◽  
P. Ligoxygakis ◽  
A. Preiss ◽  
C. Delidakis ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Ectopic Expression ◽  
Notch Pathway ◽  
Functional Relationships ◽  
Helix Loop Helix ◽  
Suppressor Of Hairless ◽  
Bhlh Genes ◽  
Enhancer Of Split ◽  
Notch Activation

The basic helix-loop-helix proteins of the Enhancer of split complex constitute a link between activation of the transmembrane receptor Notch and the resulting effects on transcription of downstream genes. The Suppressor of Hairless protein is the intermediary between Notch activation and expression of all Enhancer of split genes even though individual genes have distinct patterns of expression in imaginal discs. A comparison between the phenotypes produced by Notch, Suppressor of Hairless and Enhancer of split mutations in the wing and thorax indicate that Suppressor of Hairless and Notch requirements are indistinguishable, but that Enhancer of split activity is only essential for a subset of developmental processes involving Notch function. Likewise, the ectopic expression of Enhancer of split proteins does not reproduce all the consequences typical of ectopic Notch activation. We suggest that the Notch pathway bifurcates after the activation of Suppressor of Hairless and that Enhancer of split activity is not required when the consequence of Notch function is the transcriptional activation of downstream genes. Transcriptional activation mediated by Suppressor of Hairless and transcriptional repression mediated by Enhancer of split could provide greater diversity in the response of individual genes to Notch activity.

Notch signalling regulates veinlet expression and establishes boundaries between veins and interveins in the Drosophila wing

Development ◽  
1997 ◽  
Vol 124 (10) ◽  
pp. 1919-1928 ◽  
Author(s):  
J.F. de Celis ◽  
S. Bray ◽  
A. Garcia-Bellido
Keyword(s):  
Positive Feedback ◽  
Notch Pathway ◽  
Notch Signalling ◽  
Notch Ligand ◽  
Asymmetrical Distribution ◽  
Drosophila Wing ◽  
Split Gene ◽  
Enhancer Of Split ◽  
Notch Activation ◽  
In Cells

The veins in the Drosophila wing have a characteristic width, which is regulated by the activity of the Notch pathway. The expression of the Notch-ligand Delta is restricted to the developing veins, and coincides with places where Notch transcription is lower. We find that this asymmetrical distribution of ligand and receptor leads to activation of Notch on both sides of each vein within a territory of Delta-expressing cells, and to the establishment of boundary cells that separate the vein from adjacent interveins. In these cells, the expression of the Enhancer of split gene m beta is activated and the transcription of the vein-promoting gene veinlet is repressed, thus restricting vein differentiation. We propose that the establishment of vein thickness utilises a combination of mechanisms that include: (1) independent regulation of Notch and Delta expression in intervein and vein territories, (2) Notch activation by Delta in cells where Notch and Delta expression overlaps, (3) positive feedback on Notch transcription in cells where Notch has been activated and (4) repression of veinlet transcription by E(spl)m beta and maintenance of Delta expression by veinlet/torpedo activity.

Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 359-369 ◽  
Author(s):  
J.F. de Celis ◽  
A. Garcia-Bellido ◽  
S.J. Bray
Keyword(s):  
Imaginal Disc ◽  
Transmembrane Protein ◽  
Larval Instar ◽  
Wing Imaginal Disc ◽  
Notch Activity ◽  
Dorsal Cells ◽  
And Function ◽  
Dorsoventral Boundary ◽  
Enhancer Of Split ◽  
Notch Activation

The cells along the dorsoventral boundary of the Drosophila wing imaginal disc have distinctive properties and their specification requires Notch activity. Later in development, these cells will form the wing margin, where sensory organs and specialised trichomes appear in a characteristic pattern. We find that Notch is locally activated in these cells, as demonstrated by the restricted expression of the Enhancer of split proteins in dorsal and ventral cells abutting the D/V boundary throughout the third larval instar. Furthermore other genes identified by their involvement in Notch signaling during neurogenesis, such as Delta and Suppressor of Hairless, also participate in Notch function at the dorsoventral boundary. In addition, Serrate, a similar transmembrane protein to Delta, behaves as a ligand required in dorsal cells to activate Notch at the boundary. Notch gain-of-function alleles in which Notch activity is not restricted to the dorsoventral boundary cause miss-expression of cut and wingless and overgrowth of the disc, illustrating the importance of localised Notch activation for wing development.

her1, a zebrafish pair-rule like gene, acts downstream of notch signalling to control somite development

Development ◽  
1999 ◽  
Vol 126 (13) ◽  
pp. 3005-3014 ◽  
Author(s):  
C. Takke ◽  
J.A. Campos-Ortega
Keyword(s):  
Active Form ◽  
Notch Signalling ◽  
Paraxial Mesoderm ◽  
Presomitic Mesoderm ◽  
Essentially Normal ◽  
Early Embryos ◽  
Somite Formation ◽  
Genes Encoding ◽  
Ectopic Activation ◽  
Pair Rule

During vertebrate embryonic development, the paraxial mesoderm becomes subdivided into metameric units known as somites. In the zebrafish embryo, genes encoding homologues of the proteins of the Drosophila Notch signalling pathway are expressed in the presomitic mesoderm and expression is maintained in a segmental pattern during somitogenesis. This expression pattern suggests a role for these genes during somite development. We misexpressed various zebrafish genes of this group by injecting mRNA into early embryos. RNA encoding a constitutively active form of notch1a (notch1a-intra) and a truncated variant of deltaD [deltaD(Pst)], as well as transcripts of deltaC and deltaD, the hairy-E(spl) homologues her1 and her4, and groucho2 were tested for their effects on somite formation, myogenesis and on the pattern of transcription of putative downstream genes. In embryos injected with any of these RNAs, with the exception of groucho2 RNA, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment correctly. Activation of notch results in ectopic activation of her1 and her4. This misregulation of the expression of her genes might be causally related to the observed mesodermal defects, as her1 and her4 mRNA injections led to effects similar to those seen with notch1a-intra. deltaC and deltaD seem to function after subdivision of the presomitic mesoderm, since the her gene transcription pattern in the presomitic mesoderm remains essentially normal after misexpression of delta genes. Whereas notch signalling alone apparently does not affect myogenesis, zebrafish groucho2 is involved in differentiation of mesodermal derivatives.

scholarly journals Drosophila IMP regulates Kuzbanian to control the timing of Notch signalling in the follicle cells

2018 ◽  
Author(s):  
Weronika Fic ◽  
Celia Faria ◽  
Daniel St Johnston
Keyword(s):  
Rna Binding ◽  
Notch Pathway ◽  
Notch Signalling ◽  
Follicle Cells ◽  
Over Expression ◽  
Apical Domain ◽  
Late Endosomes ◽  
Notch Cleavage ◽  
Mirna Pathway ◽  
Notch Activation

AbstractThe timing of Drosophila egg chamber development is controlled by a germline Delta signal that activates Notch in the follicle cells to induce them to cease proliferation and differentiate. Here we report that follicle cells lacking the RNA-binding protein IMP go through one extra division due to a delay in the Delta-dependent S2 cleavage of Notch. The timing of Notch activation has previously been shown to be controlled by cis-inhibition by Delta in the follicle cells, which is relieved when the miRNA pathway represses Delta expression. imp mutants are epistatic to Delta mutants and give an additive phenotype with belle and dicer mutants, indicating that IMP functions independently of both cis-inhibition and the miRNA pathway. We find that the imp phenotype is rescued by over-expression of Kuzbanian, the metalloprotease that mediates the Notch S2 cleavage. Furthermore, Kuzbanian is not enriched at the apical membrane in imp mutants, accumulating instead in late endosomes. Thus, IMP regulates Notch signalling by controlling the localisation of Kuzbanian to the apical domain, where Notch cleavage occurs, revealing a novel regulatory step in the Notch pathway.SummaryIMP regulates Notch signalling in follicle cells by controlling Kuzbanian localisation to the apical domain, where Notch cleavage occurs, revealing a novel regulatory step in the Notch pathway.

Expression and function of decapentaplegic and thick veins during the differentiation of the veins in the Drosophila wing

Development ◽  
1997 ◽  
Vol 124 (5) ◽  
pp. 1007-1018 ◽  
Author(s):  
J.F. Celis de
Keyword(s):  
Imaginal Disc ◽  
Signal Transduction Pathways ◽  
Pupal Development ◽  
Transmembrane Receptors ◽  
Notch Ligand ◽  
Regulatory Interactions ◽  
Drosophila Wing ◽  
Signalling Molecule ◽  
And Function

The differentiation of the veins in the Drosophila wing involves the coordinate activities of several signal transduction pathways, including those mediated by the transmembrane receptors Torpedo and Notch. In this report, the role of the signalling molecule Decapentaplegic during vein differentiation has been analysed. It is shown that decapentaplegic is expressed in the pupal veins under the control of genes that establish vein territories in the imaginal disc. Decapentaplegic, acting through its receptor Thick veins, activates vein differentiation and restricts expression of both veinlet and the Notch-ligand Delta to the developing veins. Genetic combinations between mutations that increase or reduce Notch, veinlet and decapentaplegic activities suggest that the maintenance of the vein differentiation state during pupal development involves cross-regulatory interactions between these pathways.

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