Biology subjects

Gutierrez-Garcia, A.

Publications and source records attributed to Gutierrez-Garcia, A..

4 recordsLinked to original sources

bioRxiv2025

Temporal Dynamics of Azot Expression Following Traumatic Brain Injury.

Cell competition, a conserved biological process in which cells compete for survival based on relative fitness, has emerged as a critical mechanism in diverse biological contexts. Here, we investigate the role of cell competition in traumatic brain injury (TBI) by characterizing the temporal expression pattern of Azot, a key downstream effector of fitness-based selection, following injury in Drosophila melanogaster. Our findings reveal a distinct temporal profile of Azot expression post-TBI, with TUNEL assays confirming that Azot-expressing cells undergo apoptotic elimination. We demonstrate that following injury, the proportion of dying cells marked as "losers" significantly increases compared to non-injured conditions, indicating that cell competition becomes a predominant elimination mechanism during acute post-injury phases. Contrary to previous findings in neurodegenerative disease models where competition was restricted to neurons, we show that following TBI, both neurons and glia are subject to competitive elimination. Furthermore, in azot knockout conditions, we observe an accumulation of cells attempting to express Azot, suggesting impaired clearance of suboptimal cells. These findings advance our understanding of cellular quality control mechanisms following brain injury and may inform the development of novel therapeutic approaches to enhance functional recovery after TBI.

cell biology↗

bioRxiv2025

Imaging Cell Competition in Ex-Vivo Drosophila Adult Brains

Live imaging has been instrumental in understanding cellular dynamics in Drosophila tissues, but technical limitations have prevented long-term visualization of cell competition in adult brains. Here, we describe a simple ex-vivo protocol that enables extended live imaging of adult Drosophila brains for up to 32 hours. The method relies on non-supplemented Schneiders Drosophila medium and hydrophobic interactions to maintain brain stability during imaging, eliminating the need for complex culture conditions or embedding procedures. We validate this approach by studying cell competition in the optic lobes following traumatic brain injury, where cell competition is expected to occur with a peak at 48 hours after damage. We demonstrate the utility of this method by visualizing the expression of the fitness checkpoint Azot in a loser cell and its subsequent elimination. This protocol offers a versatile platform for studying cell competition and other cellular processes requiring extended observation of the adult Drosophila brain.

cell biology↗

bioRxiv2024

Heterotypic competition between cancer cells and hepatocytes generates heterogeneous context-dependent phenotypes

Competitive interactions between tumor cells and surrounding healthy cells are constantly present during the progression of a solid tumor, and their outcome has been proposed to affect the clinical behavior. Previous studies have described various mechanistic and molecular aspects that characterize this process, overall indicating that cancer cells behave as supercompetitors, which eliminate neighboring healthy cells to gain vital space for growth and infiltration of the tissue. Nevertheless, there is a lack of systematic characterization of these competitive interactions, particularly in the context of cancer in mammals. Furthermore, previous studies in the field of cell competition have primarily focused on homotypic cell competition, involving different clones of the same cell or cells deriving from the same tissue. Data are scarce regarding heterotypic cell competition between two unrelated cell types, which is particularly critical for the understanding of metastatic tumors. In this research, we study cell competition in the context of liver metastases, providing a broad characterization of this process in different relevant scenarios, including cells growing in vitro in 2D and 3D, and in vivo. Results show that in vitro, only a subset of cancer cell lines are coherently strong or moderate competitors against hepatocytes, while the remaining demonstrate poor competitiveness. The competitive proficiency can vary depending on the experimental growth system that is employed, and often predicts the phenotype of liver metastases in terms of aggressiveness and morphology. Finally, our data point towards an involvement of mechanical competition in determining the supercompetitor trait of cancer cells. Altogether, our research provides the first comprehensive characterization of heterotypic cell competition, and indicates that cancer cells possess heterogeneous competitive proficiency towards hepatocytes which can be affected by the growth conditions.

cancer biology↗

bioRxiv2024

Characterising the Modulatory Role of Ikebana in Flower-Dependent Cell Competition

Tissues encompass a quality control mechanism that promotes their optimal state. This mechanism, designated cell competition, is characterised by the elimination of suboptimal yet viable cells when they are near healthier cells within the same tissue compartment. This study explores Flower-dependent cell competition and introduces Ikebana as a novel player. The differential expression of the flower isoforms labels cells as winners or losers, influencing their fate in diverse contexts, including eye development, traumatic brain injury, and Alzheimers disease. Ikebana, ubiquitously produced in wing imaginal discs and adult brains, modulates loser cell elimination. Reduction of ikebana expression correlates with an increased number of loser cells, while its overexpression in the Alzheimers disease model reduces the number of Flower LoseB-positive cells. We suggest that Ikebana protects loser cell elimination, particularly when excessive elimination of loser cells can compromise tissue function. Thus, Ikebana might be a potential therapeutic target for modulating Flower LoseB expression.

cell biology↗