Echinoid limits R8 photoreceptor specification by inhibiting inappropriate EGF receptor signalling within R8 equivalence groups

Rawlins, Emma L.; White, Neil M.; Jarman, Andrew P.

doi:10.1242/dev.00602

Cited by 39 publications

(53 citation statements)

References 41 publications

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“…This study suggested that Echinoid acts in a separate parallel pathway to negatively regulate signalling downstream of the EGF receptor. However, more recent studies suggest that Echinoid acts at the receptor in flies (Rawlins et al, 2003), and that EGF receptor physically associates with Echinoid and mediates its tyrosine phosphorylation when the two proteins are coexpressed in cultured cells (Spencer and Cagan, 2003). In contrast with Kek1 and Argos, Echinoid does not appear to be a transcriptional target of EGF receptor, and it may act through a mechanism that involves inhibition of receptor signalling rather than receptor activation.…”

Section: Negative Modulator Proteinsmentioning

confidence: 99%

Negative regulation of ErbB family receptor tyrosine kinases

Sweeney

Carraway

2004

Br J Cancer

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Receptors of the EGF receptor or ErbB family of growth factor receptor tyrosine kinases are frequently overexpressed in a variety of solid tumours, and the aberrant activation of their tyrosine kinase activities is thought to contribute to tumour growth and progression. Much effort has been put into developing inhibitors of ErbB receptors, and both antibody and small-molecule approaches have exhibited clinical success. Recently, a number of endogenous negative regulatory proteins have been identified that suppress the signalling activity of ErbB receptors in cells. These include intracellular RING finger E3 ubiquitin ligases such as cbl and Nrdp1 that mediate ErbB receptor degradation, and may include a wide variety of secreted and transmembrane proteins that suppress receptor activation by growth factor ligands. It will be of interest to determine the extent to which tumour cells suppress these pathways to promote their progression, and whether restoration of endogenous receptor-negative regulatory pathways may be exploited for therapeutic benefit. The ErbB family of receptor tyrosine kinases, consisting of the EGF receptor, ErbB2, ErbB3 and ErbB4, directs a broad range of developmental events and contributes to the malignancy of a number of tumour types. Numerous in vivo and in vitro studies have shown that ErbB signalling plays essential roles in the development and maintenance of mammary, cardiac and neural tissues, and contributes to the development of a variety of other tissues through epithelial remodelling and differentiation. The aberrant activation of ErbB receptors in tumours can occur via mutational activation, receptor overexpression, or through tumour production of autocrine growth factor ligands.Owing to the widespread role of ErbB receptor activation in tumour growth and progression, the development of ErbB inhibitors has been a subject of intense interest. Indeed, neutralising antibodies directed towards the EGF receptor or ErbB2 are either in clinical trials or have received FDA approval for the treatment of some tumours (Arteaga, 2003). Moreover, a variety of small-molecule inhibitors are being developed to target these receptors. In this light, it is of interest to look more closely at endogenous ErbB receptor-negative regulatory pathways, the mechanisms by which tumours could overcome these checks on receptor activity, and whether these mechanisms might be employed to ultimately benefit patients.Members of the mammalian ErbB family are acted upon by EGFlike growth factor ligands, which bind to receptor extracellular domains to stimulate tyrosine kinase activity. The EGF-like domain, a 40 -60 amino-acid domain characterised by six cysteine residues forming three disulphide bonds, is a very common component of the extracellular regions of a variety of proteins encompassing a wide range of functions. Only a small subset of EGF-like proteins function as activating ligands for ErbB receptors. Despite a high degree of sequence similarity, each of the ErbB receptors appears to possess distinct bioc...

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Section: Negative Modulator Proteinsmentioning

confidence: 99%

Negative regulation of ErbB family receptor tyrosine kinases

Sweeney

Carraway

2004

Br J Cancer

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“…Loss of fred function in clones of the hypomorphic allele fred H10 yielded a similar phenotype (s.d.=13.5, P=0, MAO=89.8°). ed and fred act cooperatively in R8 specification (Rawlins et al, 2003;Spencer and Cagan, 2003) and also cooperate to ensure that ommatidia orient at precisely 90°, as fred H24 dominantly enhanced the ommatidial orientation phenotype of ed K1102 …”

Section: Resultsmentioning

confidence: 99%

“…S1 in the supplementary material). Note that some ro>ed ommatidia had the expected missing photoreceptor phenotype owing to an effect on Egfr signaling (Rawlins et al, 2003;Spencer and Cagan, 2003). In the genotypes that under-rotate, aberrant rotation was evident from the start of rotation, or between rows 4 and 5 (Fig.…”

Section: Misexpression Of Ed and Fred Generates An Underrotation Phenmentioning

confidence: 96%

“…Tissue stained with anti-Cno antibody was fixed in PLP (Takahashi et al, 1998). Discs were incubated in primary antibody overnight at 4°C at the following concentrations: mouse anti-Armadillo, 1:10 (DSHB); rabbit anti-Ed, 1:1000 [A. Jarman (Rawlins et al, 2003)]; guinea pig antiFred, 1:1000; rabbit anti-Cno, 1:500 [D. Yamamoto (Takahashi et al, 1998)]. Alexa Fluor-conjugated secondary antibodies (Molecular Probes) were used at 1:300 and incubated in the dark for 2 hours at room temperature.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Ed localizes throughout the eye imaginal disc (Bai et al, 2001;Rawlins et al, 2003), but insight into the mechanisms by which Ed might regulate ommatidial rotation necessitate a cell-by-cell and row-by-row analysis of Ed localization. Immunolocalization of the C-terminal anti-Ed antibody revealed that high levels of Ed protein localize at the apical surface of all cells in the MF and through row 1 (the arc stage; Fig.…”

Section: Ed and Fred Localize In Dynamic And Partially Overlapping Pamentioning

confidence: 99%

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The cell adhesion molecules Echinoid and Friend of Echinoid coordinate cell adhesion and cell signaling to regulate the fidelity of ommatidial rotation in theDrosophilaeye

2009

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Directed cellular movements are a universal feature of morphogenesis in multicellular organisms. Differential adhesion between the stationary and motile cells promotes these cellular movements to effect spatial patterning of cells. A prominent feature of Drosophila eye development is the 90°rotational movement of the multicellular ommatidial precursors within a matrix of stationary cells. We demonstrate that the cell adhesion molecules Echinoid (Ed) and Friend of Echinoid (Fred) act throughout ommatidial rotation to modulate the degree of ommatidial precursor movement. We propose that differential levels of Ed and Fred between stationary and rotating cells at the initiation of rotation create a permissive environment for cell movement, and that uniform levels in these two populations later contribute to stopping the movement. Based on genetic data, we propose that ed and fred impart a second, independent, 'brake-like' contribution to this process via Egfr signaling. Ed and Fred are localized in largely distinct and dynamic patterns throughout rotation. However, ed and fred are required in only a subset of cells -photoreceptors R1, R7 and R6 -for normal rotation, cells that have only recently been linked to a role in planar cell polarity (PCP). This work also provides the first demonstration of a requirement for cone cells in the ommatidial rotation aspect of PCP. ed and fred also genetically interact with the PCP genes, but affect only the degree-of-rotation aspect of the PCP phenotype. Significantly, we demonstrate that at least one PCP protein, Stbm, is required in R7 to control the degree of ommatidial rotation.

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Salivary analysis in oral cancer patients

Bahar

Feinmesser

Shpitzer

et al. 2006

Cancer

153

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Morphogenesis of the Drosophila embryonic trachea involves a stereotyped pattern of epithelial tube branching and fusion. Here, we report unexpected phenotypes resulting from maternal and zygotic (M/Z) loss of the homophilic cell adhesion molecule Echinoid (Ed), as well as the subcellular localization of Ed in the trachea. edM/Z embryos have convoluted trachea reminiscent of septate junction (SJ) and luminal matrix mutants. However, Ed does not localize to SJs, and edM/Z embryos have intact SJs and show normal luminal accumulation of the matrix‐modifying protein Vermiform. Surprisingly, tracheal length is not increased in edM/Z mutants, but a previously undescribed combination of reduced intersegmental spacing and deep epidermal grooves produces a convoluted tracheal phenotype. In addition, edM/Z mutants have unique fusion defects involving supernumerary fusion cells, ectopic fusion events and atypical branch breaks. Tracheal‐specific expression of Ed rescues these fusion defects, indicating that Ed acts in trachea to control fusion cell fate. Developmental Dynamics 239:2509–2519, 2010. © 2010 Wiley‐Liss, Inc.

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Echinoid limits R8 photoreceptor specification by inhibiting inappropriate EGF receptor signalling within R8 equivalence groups

Cited by 39 publications

References 41 publications

Negative regulation of ErbB family receptor tyrosine kinases

Negative regulation of ErbB family receptor tyrosine kinases

The cell adhesion molecules Echinoid and Friend of Echinoid coordinate cell adhesion and cell signaling to regulate the fidelity of ommatidial rotation in theDrosophilaeye

Salivary analysis in oral cancer patients

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