scholarly journals The Drosophila functional Smad suppressing element fuss, a homologue of the human Skor genes, retains pro-oncogenic properties of the Ski/Sno family

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262360
Author(s):  
Mathias Rass ◽  
Laura Gizler ◽  
Florian Bayersdorfer ◽  
Christoph Irlbeck ◽  
Matthias Schramm ◽  
...  

Over the years Ski and Sno have been found to be involved in cancer progression e.g. in oesophageal squamous cell carcinoma, melanoma, oestrogen receptor-positive breast carcinoma, colorectal carcinoma, and leukaemia. Often, their prooncogenic features have been linked to their ability of inhibiting the anti-proliferative action of TGF-ß signalling. Recently, not only pro-oncogenic but also anti-oncogenic functions of Ski/Sno proteins have been revealed. Besides Ski and Sno, which are ubiquitously expressed other members of Ski/Sno proteins exist which show highly specific neuronal expression, the SKI Family Transcriptional Corepressors (Skor). Among others Skor1 and Skor2 are involved in the development of Purkinje neurons and a mutation of Skor1 has been found to be associated with restless legs syndrome. But neither Skor1 nor Skor2 have been reported to be involved in cancer progression. Using overexpression studies in the Drosophila eye imaginal disc, we analysed if the Drosophila Skor homologue Fuss has retained the potential to inhibit differentiation and induce increased proliferation. Fuss expressed in cells posterior to the morphogenetic furrow, impairs photoreceptor axon pathfinding and inhibits differentiation of accessory cells. However, if its expression is induced prior to eye differentiation, Fuss might inhibit the differentiating function of Dpp signalling and might maintain proliferative action of Wg signalling, which is reminiscent of the Ski/Sno protein function in cancer.

2018 ◽  
Author(s):  
Bradly Alicea ◽  
Thomas E. Portegys ◽  
Diana Gordon ◽  
Richard Gordon

AbstractWe can improve our understanding of biological processes through the use of computational and mathematical modeling. One such morphogenetic process (ommatidia formation in the Drosophila eye imaginal disc) provides us with an opportunity to demonstrate the power of this approach. We use a high-resolution image that catches the spatially- and temporally-dependent process of ommatidia formation in the act. This image is converted to quantitative measures and models that provide us with new information about the dynamics and geometry of this process. We approach this by addressing three computational hypotheses, and provide a publicly-available repository containing data and images for further analysis. Potential spatial patterns in the morphogenetic furrow and ommatidia are summarized, while the ommatidia cells are projected to a spherical map in order to identify higher-level spatiotemporal features. In the conclusion, we discuss the implications of our approach and findings for developmental complexity and biological theory.


Development ◽  
2001 ◽  
Vol 128 (14) ◽  
pp. 2689-2697 ◽  
Author(s):  
Justin P. Kumar ◽  
Kevin Moses

The onset of pattern formation in the developing Drosophila retina begins with the initiation of the morphogenetic furrow, the leading edge of a wave of retinal development that transforms a uniform epithelium, the eye imaginal disc into a near crystalline array of ommatidial elements. The initiation of this wave of morphogenesis is under the control of the secreted morphogens Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg). We show that the Epidermal Growth Factor Receptor and Notch signaling cascades are crucial components that are also required to initiate retinal development. We also show that the initiation of the morphogenetic furrow is the sum of two genetically separable processes: (1) the ‘birth’ of pattern formation at the posterior margin of the eye imaginal disc; and (2) the subsequent ‘reincarnation’ of retinal development across the epithelium.


Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3233-3240 ◽  
Author(s):  
D.I. Strutt ◽  
M. Mlodzik

Pattern formation in the eye imaginal disc of Drosophila occurs in a wave that moves from posterior to anterior. The anterior edge of this wave is marked by a contracted band of cells known as the morphogenetic furrow, behind which photoreceptors differentiate. The movement of the furrow is dependent upon the secretion of the signalling protein Hedgehog (Hh) by more posterior cells, and it has been suggested that Hh acts as an inductive signal to induce cells to enter a furrow fate and begin differentiation. To further define the role of Hh in this process, we have analysed clones of cells lacking the function of the smoothened (smo) gene, which is required for transduction of the Hh signal and allows the investigation of the autonomous requirement for hh signalling. These experiments demonstrate that the function of hh in furrow progression is indirect. Cells that cannot receive/transduce the Hh signal are still capable of entering a furrow fate and differentiating normally. However, hh is required to promote furrow progression and regulate its rate of movement across the disc, since the furrow is significantly delayed in smo clones.


Development ◽  
1997 ◽  
Vol 124 (13) ◽  
pp. 2499-2506 ◽  
Author(s):  
A.C. Zelhof ◽  
N. Ghbeish ◽  
C. Tsai ◽  
R.M. Evans ◽  
M. McKeown

Many of the same genes needed for proper eye and limb development in vertebrates, such as hairy, hedgehog, patched and cyclic AMP-dependent protein kinase A, are responsible for patterning Drosophila imaginal discs, the tissues that will give rise to the adult cuticle structures. This is well demonstrated in the control of morphogenetic furrow movement and differentiation in the eye imaginal disc. We report that ultraspiracle, the gene encoding the Drosophila cognate of the Retinoid X Receptor, is required for normal morphogenetic furrow movement and ommatidial cluster formation. Examination of the expression of genes involved in regulating the furrow suggests that ultraspiracle defines a novel regulatory pathway in eye differentiation.


Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 559-567 ◽  
Author(s):  
F. Chanut ◽  
U. Heberlein

Morphogenesis in the Drosophila retina initiates at the posterior margin of the eye imaginal disc by an unknown mechanism. Upon initiation, a wave of differentiation, its forward edge marked by the morphogenetic furrow (MF), proceeds anteriorly across the disc. Progression of the MF is driven by hedgehog (hh), expressed by differentiating photoreceptor cells. The TGF-beta homolog encoded by decapentaplegic (dpp) is expressed at the disc's posterior margin prior to initiation and in the furrow, under the control of hh, during MF progression. While dpp has been implicated in eye disc growth and morphogenesis, its precise role in retinal differentiation has not been determined. To address the role of dpp in initiation and progression of retinal differentiation we analyzed the consequences of reduced and increased dpp function during eye development. We find that dpp is not only required for normal MF initiation, but is sufficient to induce ectopic initiation of differentiation. Inappropriate initiation is normally inhibited by wingless (wg). Loss of dpp function is accompanied by expansion of wg expression, while increased dpp function leads to loss of wg transcription. In addition, dpp is required to maintain, and sufficient to induce, its own expression along the disc's margins. We postulate that dpp autoregulation and dpp-mediated inhibition of wg expression are required for the coordinated regulation of furrow initiation and progression. Finally, we show that in the later stages of retinal differentiation, reduction of dpp function leads to an arrest in MF progression.


Fly ◽  
2010 ◽  
Vol 4 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Marion Silies ◽  
Yeliz Yuva-Aydemir ◽  
Sigrídur Rut Franzdottir ◽  
Christian Klämbt

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2046 ◽  
Author(s):  
Valerio Izzi ◽  
Martin N. Davis ◽  
Alexandra Naba

The extracellular matrix (ECM) is a master regulator of all cellular functions and a major component of the tumor microenvironment. We previously defined the “matrisome” as the ensemble of genes encoding ECM proteins and proteins modulating ECM structure or function. While compositional and biomechanical changes in the ECM regulate cancer progression, no study has investigated the genomic alterations of matrisome genes in cancers and their consequences. Here, mining The Cancer Genome Atlas (TCGA) data, we found that copy number alterations and mutations are frequent in matrisome genes, even more so than in the rest of the genome. We also found that these alterations are predicted to significantly impact gene expression and protein function. Moreover, we identified matrisome genes whose mutational burden is an independent predictor of survival. We propose that studying genomic alterations of matrisome genes will further our understanding of the roles of this compartment in cancer progression and will lead to the development of innovative therapeutic strategies targeting the ECM.


Oncogene ◽  
1999 ◽  
Vol 18 (48) ◽  
pp. 6767-6775 ◽  
Author(s):  
Masamitsu Yamaguchi ◽  
Fumiko Hirose ◽  
Yoshihiro H Inoue ◽  
Michina Shiraki ◽  
Yuko Hayashi ◽  
...  

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