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1. Applying molecular communication theory to estimate information loss in cell signal transduction: an approach based on cancer transcriptomics

   https://doi.org/10.1145/3233188.3233202  

   Sakkaff, Zahmeeth ; Immaneni, Aditya ; Pierobon, Massimiliano ( September 2018 , NANOCOM '18 Proceedings of the 5th ACM International Conference on Nanoscale Computing and Communication)

   Signal transduction pathways are chemical communication channels embedded in biological cells, and they propagate information from the environment to regulate cell growth and proliferation, among other cell's behaviors. Disruptions in the normal functionalities of these channels, mostly resulting from mutations in the underlying genetic code, can be leading causes of diseases, such as cancer. Motivated by the increasing availability of public data on genetic code expression in cell tissue samples, i.e., transcriptomics, and the emerging field of molecular communication, a novel data-driven approach based on experimental data mining and communication theory is proposed in this paper. This approach is an alternative to existing computational models of these pathways in the context of cancer, which often appear to oversimplify the complexity of the underlying mechanisms. In contrast, a computational methodology is here derived to estimate the difference in information propagation performance of signal transduction pathways in healthy and diseased cells, solely based on transcriptomic data. This methodology is built upon a molecular communication abstraction of information flow through the pathway and its correlation with the expression of the underlying DNA genes. Numerical results are presented for a case study based on the JAK-STAT pathway in kidney cancer, and correlated with the occurrence of pathway gene mutations in the available data. 

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2. The ETS-transcription factor Pointed is sufficient to regulate the posterior fate of the follicular epithelium

   https://doi.org/10.1242/dev.189787  

   Stevens, Cody A. ; Revaitis, Nicole T. ; Caur, Rumkan ; Yakoby, Nir ( November 2020 , Development)

   null (Ed.)

   The Janus-kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway regulates the anterior posterior axis of the Drosophila follicle cells. In the anterior, it activates the bone morphogenetic protein (BMP) signaling pathway through expression of the BMP ligand, decapentaplegic (dpp). In the posterior, JAK/STAT works with the epidermal growth factor receptor (EGFR) pathway to express the T-box transcription factor midline (mid). While MID is necessary in establishing the posterior fate of the egg chamber, we show that it is not sufficient to determine a posterior fate. The ETS-transcription factor pointed (pnt) is expressed in an overlapping domain to mid in the follicle cells. This study shows that pnt is upstream of mid, and it is sufficient to induce a posterior fate in the anterior end, which is characterized by the induction of mid, the prevention of the stretched cells formation, and the abrogation of border cells migration. We demonstrate that the anterior BMP signaling is abolished by PNT through dpp repression. However, ectopic DPP cannot rescue this repression, suggesting additional targets of PNT participate in the posterior fate determination. 

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3. Tumor models in various Drosophila tissues

   https://doi.org/10.1002/wsbm.1525  

   Gong, Shangyu ; Zhang, Yichi ; Tian, Aiguo ; Deng, Wu‐Min ( March 2021 , WIREs Mechanisms of Disease)

   The development of cancer is a complex multistage process. Over the past few decades, the model organismDrosophila melanogasterhas been crucial in identifying cancer‐related genes and pathways and elucidating mechanisms underlying growth regulation in development. Investigations usingDrosophilahas yielded new insights into the molecular mechanisms involved in tumor initiation and progression. In this review, we describe various tumor models that have been developed in recent years using differentDrosophilatissues, such as the imaginal tissue, the neural tissue, the gut, the ovary, and hematopoietic cells. We discuss underlying genetic alterations, cancer‐like characteristics, as well as similarities and key differences among these models. We also discuss how disruptions in stem cell division and differentiation result in tumor formation in diverse tissues, and highlight new concepts developed using the fly model to understand context‐dependent tumorigenesis. We further discuss the progress made inDrosophilato explore tumor–host interactions that involve the innate immune response to tumor growth and the cachexia wasting phenotype.

   This article is categorized under:

   Cancer > Genetics/Genomics/Epigenetics

   Cancer > Stem Cells and Development

   Cancer > Molecular and Cellular Physiology

    

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4. From network analysis to experimental validation: identification of regulators of non-muscle myosin II contractility using the folded-gastrulation signaling pathway

   https://doi.org/10.1186/s12860-023-00492-3  

   Zhao, Andy ; Varady, Sophia ; O’Kelley-Bangsberg, Madelyn ; Deng, Vicki ; Platenkamp, Amy ; Wijngaard, Petra ; Bern, Miriam ; Gormley, Wyatt ; Kushkowski, Elaine ; Thompson, Kat ; et al ( October 2023 , BMC Molecular and Cell Biology)

   The morphogenetic process of apical constriction, which relies on non-muscle myosin II (NMII) generated constriction of apical domains of epithelial cells, is key to the development of complex cellular patterns. Apical constriction occurs in almost all multicellular organisms, but one of the most well-characterized systems is the Folded-gastrulation (Fog)-induced apical constriction that occurs inDrosophila. The binding of Fog to its cognizant receptors Mist/Smog results in a signaling cascade that leads to the activation of NMII-generated contractility. Despite our knowledge of key molecular players involved in Fog signaling, we sought to explore whether other proteins have an undiscovered role in its regulation. We developed a computational method to predict unidentified candidate NMII regulators using a network of pairwise protein–protein interactions called an interactome. We first constructed aDrosophilainteractome of over 500,000 protein–protein interactions from several databases that curate high-throughput experiments. Next, we implemented several graph-based algorithms that predicted 14 proteins potentially involved in Fog signaling. To test these candidates, we used RNAi depletion in combination with a cellular contractility assay inDrosophilaS2R + cells, which respond to Fog by contracting in a stereotypical manner. Of the candidates we screened using this assay, two proteins, the serine/threonine phosphatase Flapwing and the putative guanylate kinase CG11811 were demonstrated to inhibit cellular contractility when depleted, suggestive of their roles as novel regulators of the Fog pathway.

    

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5. Comparative transcriptome analyses of the Drosophila pupal eye

   https://doi.org/10.1093/g3journal/jkaa003  

   DeAngelis, Miles W ; Coolon, Joseph D ; Johnson, Ruth I ( January 2021 , G3 Genes|Genomes|Genetics)

   Lott, S (Ed.)

   Abstract Tissue function is dependent on correct cellular organization and behavior. As a result, the identification and study of genes that contribute to tissue morphogenesis is of paramount importance to the fields of cell and developmental biology. Many of the genes required for tissue patterning and organization are highly conserved between phyla. This has led to the emergence of several model organisms and developmental systems that are used to study tissue morphogenesis. One such model is the Drosophila melanogaster pupal eye that has a highly stereotyped arrangement of cells. In addition, the pupal eye is postmitotic that allows for the study of tissue morphogenesis independent from any effects of proliferation. While the changes in cell morphology and organization that occur throughout pupal eye development are well documented, less is known about the corresponding transcriptional changes that choreograph these processes. To identify these transcriptional changes, we dissected wild-type Canton S pupal eyes and performed RNA-sequencing. Our analyses identified differential expression of many loci that are documented regulators of pupal eye morphogenesis and contribute to multiple biological processes including signaling, axon projection, adhesion, and cell survival. We also identified differential expression of genes not previously implicated in pupal eye morphogenesis such as components of the Toll pathway, several non-classical cadherins, and components of the muscle sarcomere, which could suggest these loci function as novel patterning factors. 

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