Egfr/Ras pathway mediates interactions between peripodial and disc proper cells in<i>Drosophila</i>wing discs

Pallavi, SK; Shashidhara, L. S.

doi:10.1242/dev.00719

Cited by 53 publications

(69 citation statements)

References 47 publications

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“…Together the data support the idea that CG4382 functions as a negative regulator of vein development, which is repressed by a high level of Egfr signaling. The expression of CG4382 in the peripodial membrane overlying the disc proper suggests that its function in venation appears to involve communication between two cell layers, as has been noted for patterning of the major regions of the wing disc (Baena-Lopez et al 2003;Pallavi and Shashidhara 2003). Our results suggest the peripodial membrane may also have a more specific role in vein patterning.…”

Section: Cg6234supporting

confidence: 73%

New Negative Feedback Regulators of Egfr Signaling inDrosophila

et al. 2012

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The highly conserved epidermal growth factor receptor (Egfr) pathway is required in all animals for normal development and homeostasis; consequently, aberrant Egfr signaling is implicated in a number of diseases. Genetic analysis of Drosophila melanogaster Egfr has contributed significantly to understanding this conserved pathway and led to the discovery of new components and targets. Here we used microarray analysis of third instar wing discs, in which Egfr signaling was perturbed, to identify new Egfrresponsive genes. Upregulated transcripts included five known targets, suggesting the approach was valid. We investigated the function of 29 previously uncharacterized genes, which had pronounced responses. The Egfr pathway is important for wing-vein patterning and using reverse genetic analysis we identified five genes that showed venation defects. Three of these genes are expressed in vein primordia and all showed transcriptional changes in response to altered Egfr activity consistent with being targets of the pathway. Genetic interactions with Egfr further linked two of the genes, Sulfated (Sulf1), an endosulfatase gene, and CG4096, an A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS) gene, to the pathway. Sulf1 showed a strong genetic interaction with the neuregulin-like ligand vein (vn) and may influence binding of Vn to heparan-sulfated proteoglycans (HSPGs). How Drosophila Egfr activity is modulated by CG4096 is unknown, but interestingly vertebrate EGF ligands are regulated by a related ADAMTS protein. We suggest Sulf1 and CG4096 are negative feedback regulators of Egfr signaling that function in the extracellular space to influence ligand activity.

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Section: Cg6234supporting

confidence: 73%

New Negative Feedback Regulators of Egfr Signaling inDrosophila

et al. 2012

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“…To investigate how BM remodeling contributes to tissue development, we chose to inhibit MMP function by targeted overexpression of the Drosophila tissue inhibitor of metalloproteases (TIMP) (14) using the UAS/GAL4 system (15). Overexpression of TIMP in the larval fat body, driven by Lsp2-GAL4 (Lsp2ϾTIMP) (16) and in the peripodial epithelium of the larval wing imaginal discs, by Ubx-GAL4 (UbxϾTIMP) (17), resulted in striking phenotypes that we focused on for further characterization [ Fig. 1 and supporting information (SI) Fig.…”

Section: Reduction Of Mmp Activities Results In Disc Eversionmentioning

confidence: 99%

Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion

Srivastava

Pastor-Pareja

Igaki

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

186

245

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Organ and tissue integrity is often maintained in animals by a specialized extracellular matrix structure called the basement membrane (BM). Accumulated evidence indicates that BM remodeling occurs during development and tumor invasion. Although the BM organizes and functions at the organ level, most past studies have explored its biochemical and in vitro properties. In this study, we monitor the BM in vivo during developmental tissue invasion for disc eversion and tumor invasion in Drosophila and modulate BM integrity with genetic alterations affecting either the whole organism or the targeted discs or tumors. We observe that the degradation of BM by the discs or the tumors is an early event during invasion processes and that preventing BM degradation completely blocks both tissue and tumor invasion, indicating that modulation of BM is essential for developmental and tumor invasion. Furthermore, elements of the invasion machinery, including JNK-induced matrix metalloproteinase (MMP) expression, are shared by both disc eversion and tumor invasion processes. Moreover, we show that although expression of MMP inhibitor, TIMP, is sufficient to halt developmental invasion, inhibition of proteases by both TIMP and RECK are required to block tumor invasion. These data suggest that tumor cells have a more robust invasion mechanism and could acquire metastatic behavior by co-opting developmental invasion programs. This type of co-option may be a general feature contributing to the progression of tumors. Finally, although past efforts using MMP inhibitors have not yielded much success, our results strongly argue that BM modulation could be a critical target for cancer therapy.developmental invasion ͉ JNK signaling ͉ tumor metastasis ͉ matrix metalloproteinase

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“…of EGFR/RAS pathway in the wing disc PM affects wingnotum/hinge decision in DP (Pallavi and Shashidhara, 2003). It has also been observed that puckered (puc), a negative regulator of the Jun N-terminal kinase (JNK) pathway, and hemipterous (hep), which encodes Drosophila JNK-kinase, are expressed in cells at the medial edge of the wing disc PM (Agnes et al, 1999).…”

mentioning

confidence: 99%

Signaling interactions between squamous and columnar epithelia of the Drosophila wing disc

Pallavi

Shashidhara

2005

Journal of Cell Science

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Understanding the interactions between distinct epithelial cells would help us to understand the development of tissues. Drosophila imaginal discs, which are made up of two types of epithelial cells, provide good model systems for such studies. The disc proper or the columnar epithelial cells are apposed to a layer of squamous epithelial cells (the peripodial membrane). We have examined organization of peripodial and disc proper cells vis-à-vis their polarity since cell polarity plays an important role in the polarized transport of signaling molecules. With the help of polarity-specific cell markers, we have observed that apical surfaces of peripodial and disc proper cells face each other. This provides the cellular basis for the recently demonstrated signaling interactions between peripodial and disc proper cells during disc patterning. We also report significant similarities as well as differences between peripodial and disc proper cells in Engrailed-dependent wingdisc-patterning events, which make them an appropriate model system for studying the mechanism of diffusion of signal molecules, such as Hedgehog. Results with wild-type and two mutant forms of Hedgehog suggest that direct cell-cell contact is a requirement for the movement of wild-type Hedgehog signal and reconfirm that cholesterol-modification of Hedgehog makes it a short-range signaling molecule by restricting its movement.

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Egfr/Ras pathway mediates interactions between peripodial and disc proper cells inDrosophilawing discs

Cited by 53 publications

References 47 publications

New Negative Feedback Regulators of Egfr Signaling inDrosophila

New Negative Feedback Regulators of Egfr Signaling inDrosophila

Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion

Signaling interactions between squamous and columnar epithelia of the Drosophila wing disc

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