Biology subjects

Garcia-Arias, J. M.

Publications and source records attributed to Garcia-Arias, J. M..

3 recordsLinked to original sources

bioRxiv2025

Dpp and Immune Response Pathways Factors Mediate Paracrine Induction of Senescent Cells in Drosophila

Transition toward senescence is a cellular response to different stressors like ionizing radiation, telomere shortening or oncogene activation. This phenomenon is evolutionarily conserved across species, from insects to humans. Senescent cells (SCs) permanently withdraw from the cell cycle and undergo a series of physiological changes, most notably the acquisition of a robust secretory activity characterized by the release of numerous molecules, including cytokines, chemokines, and metalloproteinases. Through this program, termed Senescence-Associated Secretory Phenotype (SASP), SCs actively communicate with and influence their microenvironment. In mammalian tissues the number of SCs increases with age and their accumulation has been proposed to contribute to several age-associated pathologies. Studies in vertebrate systems have demonstrated that new SCs can arise through paracrine signaling from pre-existing SCs, a process that requires the activity of Transforming Growth Factor {beta} (TGF-{beta}). We have investigated the phenomenon of paracrine recruitment of SCs in the Drosophila wing disc. Our results show that an initial stress event induces a primary wave of SCs, comprising approximately 10% of the target cell population. Subsequently, a second wave of SCs emerges through paracrine signaling from the initial cohort, increasing the overall proportion of SCs to about 24%. The formation of this second wave is mediated by the growth factor Decapentaplegic (Dpp), the Drosophila ortholog of TGF-{beta}. Dpp activates a non-canonical signaling route in non-SCs, driving their conversion to a senescent state. This novel branch of the Dpp pathway engages several components of the innate immune response. Collectively, these findings underscore the evolutionary conservation of senescence-associated signaling networks and suggest that paracrine amplification of senescence may play a role in tumorigenesis and age-related diseases.

cell biology↗

bioRxiv2025

Cytoneme-mediated signalling coordinates the development of glial cells and neurons in the Drosophila eye

Effective cell communication is essential for the development and maintenance of the nervous system, where neurons and glial cells must interact closely. While cytoneme-mediated signalling is well-documented in various biological contexts, its role in coordinating neuron-glia development remains poorly understood. In this study, we investigated the function of cytonemes in neuron-glia coordination using the Drosophila eye imaginal disc as a model. This is a well-established system for examining the orchestrated development of glial and neuronal cells. Our results reveal that glial cells produce two distinct types of cytonemes based on their spatial orientation: one set extends toward nascent photoreceptors, while the other targets the morphogenetic furrow (MF). We have characterised the dynamics of glial cytonemes and demonstrated that disrupting these structures has a significant impact on glial cell migration and differentiation. This highlights the critical role of cytoneme-mediated signalling in regulating glial behaviour. Our findings also demonstrate that cytoneme function is essential for activating the Hedgehog (Hh) pathway in glial cells, with Hh ligand produced by photoreceptors. This pathway is necessary for glial differentiation, uncovering a previously unrecognised role for Hh signalling in this process. Overall, our results suggest that cytoneme-mediated Hh signalling is key to coordinating the development of both glial and neuronal populations.

developmental biology↗

bioRxiv2023

LACK OF APOPTOSIS CAUSES CELLULAR SENESCENCE AND TUMORIGENESIS IN DROSOPHILA EPITHELIAL CELLS

Programmed cell death (apoptosis) is a homeostasis program of animal tissues designed to remove cells that are unwanted or are damaged by physiological insults. To assess the functional role of apoptosis we have studied the consequences of subjecting Drosophila epithelial cells defective in apoptosis to stress or genetic perturbations that normally cause massive cell death. We find that many of those cells acquire persistent activity of the JNK pathway, which drives them into senescent status, characterized by arrest of cell division, cell hypertrophy, Senescent Associated {beta}-gal activity (SA-{beta}-gal), ROS production, Senescent Associated Secretory Phenotype (SASP) and migratory behaviour. We have identified two classes of senescent cells in the wing disc: 1) those that localize to the appendage part of the disc, express the upd, wg and dpp signalling genes and generate tumour overgrowths, and 2) those located in the thoracic region do not express wg and dpp nor they induce tumour overgrowths. Whether to become tumorigenic or non-tumorigenic depends on the original identity of the cell prior to the transformation. We also find that the p53 gene contributes to senescence by enhancing the activity of JNK.

developmental biology↗