Biology subjects

Logeay, R.

Publications and source records attributed to Logeay, R..

4 recordsLinked to original sources

bioRxiv2025

E(spl)m4 Directly Antagonizes Traf4 to Inhibit JNK Signaling in Drosophila

TRAF proteins are adaptor proteins that participate in signal transduction downstream of the Toll or TNF receptors and could elicit E3-Ubiquitin Ligase activity. They have been implicated in multiple processes during signal transduction, inflammation, and morphogenesis. In Drosophila, Traf4 has been implicated in the regulation of JNK signaling and cell death as well as Adherens Junctions regulation. Using overexpression approaches, we show here that Traf4 promotes JNK and caspase activation, as well as junctional E-Cadherin/ {beta}-Catenin depletion, resulting in epithelial cell delamination. Using biochemical, modelling, and functional genetics approaches, we further show that the Bearded-type small protein E(spl)m4 binds to Traf4, and inhibits its downstream signaling towards JNK activation and cell delamination, without affecting the effects of Traf4 on Adherens Junctions. Thus, this study identifies an endogenous peptide inhibiting Traf4 signaling, potentially by blocking Traf4 trimerization.

developmental biology↗

bioRxiv2021

PECAn, a pipeline for image processing and statistical analysis of complex mosaic 3D tissues

Investigating organ biology requires sophisticated methodologies to induce genetically distinct clones within a tissue. Microscopic analysis of such samples produces information-rich 3D images. However, the 3D nature and spatial anisotropy of clones makes sample analysis challenging and slow and limits the amount of information that can be extracted manually. Here we have developed a pipeline for image processing and statistical data analysis which automatically extracts sophisticated parameters from complex multi-genotype 3D images. The pipeline includes data handling, machine-learning-enabled segmentation, multivariant statistical analysis, and graph generation. This enables researchers to run rigorous analyses on images and videos at scale and in a fraction of the time, without requiring programming skills. We demonstrate the power of this pipeline by applying it to the study of Minute cell competition. We find an unappreciated sexual dimorphism in Minute competition and identify, by statistical regression analysis, tissue parameters that model and predict competitive death.

cell biology↗

bioRxiv2021

Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status

Cell competition induces the elimination of less-fit "loser" cells by fitter "winner" cells. In Drosophila, cells heterozygous mutant in ribosome genes, Rp/+, known as Minutes, are eliminated via cell competition by wild-type cells. Rp/+ cells display proteotoxic stress and the oxidative stress response, which drive the loser status. Minute cell competition also relies on the activities of the transcription factors Irbp18 and Xrp1, however how these contribute to the loser status is partially understood. Here, we show that Irbp18 and Xrp1 induce the loser status by promoting proteotoxic stress. We find that Xrp1 is necessary for Rp/+ - induced proteotoxic stress and is sufficient to induce proteotoxic stress in otherwise wild-type cells. Xrp1 is also induced downstream of proteotoxic stress and required for the competitive elimination of cells suffering from proteotoxic stress. Our data suggests that a feed-forward loop between Xrp1, proteotoxic stress, and Nrf2 drives Minute cells to become losers.

genetics↗

bioRxiv2020

Loss of epithelial polarity redirects Notch signaling and triggers a Xrp1 response during neoplastic growth in Drosophila

Aggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch dedicated transcription factor. The Notch-dependent neoplasms require however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1, and bZIP factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally our work highlights some Notch/scrib specificities, in particular the role of the PAR domain containing bZIP transcription factor and Notch direct target Pdp1 for neoplastic growth.

developmental biology↗