Biology subjects

Morata, G.

Publications and source records attributed to Morata, G..

5 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

The Homeodomain-interacting protein kinase Hipk promotes apoptosis by stabilizing the active form of Dronc

Members of the evolutionarily conserved homeodomain-interacting protein kinase (Hipk) family play a critical role in regulating essential signalling pathways involved in growth, differentiation, and apoptosis. While vertebrates have multiple hipk genes, Drosophila contains a single hipk ortholog, what facilitates functional analysis. We find that hipk is necessary for the stabilization of the initiator caspase Dronc, thus enhancing the two Dronc activities in apoptotic scenarios: the induction of the caspase cascade, and the reinforcement of JNK signalling pathway. Conversely, our data suggest that Dronc also raises the expression levels of Hipk, thereby reinforcing the apoptotic response. These findings significantly enhance our understanding of caspase regulation and position Hipk as a promising target for modulating caspase activity in a variety of biological contexts.

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↗

bioRxiv2022

Size compensation in Drosophila after generalised cell death

Regeneration is a response mechanism to restore tissues that have been damaged or lost by mechanical or physiological insults. We are studying in the wing imaginal disc of Drosophila the regenerative response to a high dose of Ionizing Radiation (IR), which we estimate kills at least 35% of the cells. After such treatment irradiated discs are able to restore normal size and shape, indicating there is a mechanism to replace the lost cells. We have tested the role of the Jun N-terminal Kinase (JNK), Janus Kinase (JAK/STAT) and Wingless (Wg) pathways, which have been shown to promote cell proliferation in regenerating tissues. We find that there is size compensation after IR in the absence of function of these pathways, strongly suggesting that they are not necessary for the compensation. We also find that the proliferation rate is not increased after IR. We argue that after generalized death caused by IR there is not a specific mechanism to promote cell proliferation. The irradiated discs suffer a developmental delay and then resume growth at normal rate until they reach the final stereotyped size. The delay appears to be associated with a developmental reversion, as irradiated discs undergo rejuvenation towards an earlier developmental stage. The response to generalized damage is fundamentally different from that to localized damage, which requires activity of JNK and Wg.

developmental biology↗

bioRxiv2018

A refutation to ‘A new A-P compartment boundary and organizer in holometabolous insect wings.’

We respond to a recent report by Abbasi and Marcus who present two main findings: first they argue that there is an organiser and a compartment boundary within the posterior compartment of the butterfly wing. Second, they present evidence for a previously undiscovered lineage boundary near wing vein 5 in Drosophila, a boundary that delineates a \"far posterior\" compartment. Clones of cells were marked with the yellow mutation and they reported that these clones always fail to cross a line close to vein 5 on the Drosophila wing. In our hands yellow proved an unusable marker for clones in the wing blade and therefore we reexamined the matter. We marked clones of cells with multiple wing hairs or forked and found a substantial proportion of these clones cross the proposed lineage boundary near vein 5, in conflict with their findings and conclusion. As internal controls we showed that these same clones respect the other two well established compartment boundaries: the anteroposterior compartment boundary is always respected. The dorsoventral boundary is mostly respected, and is crossed only by clones that are induced early in development, consistent with many reports. We question the validity of Abbasi and Marcus conclusions regarding the butterfly wing but present no new data.\n\nArising from: R. Abbasi and J. M. Marcus Sci. Rep. 7, 16337 (2017); https://doi.org/10.1038/s41598-017-16553-5

developmental biology↗