Biology subjects

Azpiazu, N.

Publications and source records attributed to Azpiazu, N..

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↗

bioRxiv2024

A function of Spalt proteins in heterochromatin organization and maintenance of genomic DNA integrity

The phylogenetically conserved Spalt proteins regulate gene expression and participate in a variety of cell fate choices during multicellular development, generally acting as transcriptional repressors in different gene regulatory networks. Paradoxically, besides their roles as DNA sequence-specific transcription factors, Spalt proteins show a consistent localization to heterochromatic regions. They can act through interactions with the Nucleosome remodeling and deacetylase complex (NuRD) to promote closing of open chromatin domains, but their activities as epigenetic regulators also rely on interactions with DNA Methyltransferases or with the Lysine-specific histone demethylase LSD1, suggesting that they can participate in multiple regulatory mechanisms. Here we describe several major consequences of loss of spalt function in Drosophila cells, including changes in chromatin accessibility affecting mostly pericentromeric heterochromatin, the generation of DNA damage, alterations in the localization of chromosomes within the nucleus in polyploid cells of the salivary glands and miss-expression of transposable elements. We suggest that most of these effects are related to roles of Spalt proteins in the regulation of heterochromatin formation. We propose that Drosophila Spalt proteins have two complementary functions, acting as sequence-specific transcriptional repressors on specific target genes and regulating more global gene silencing through the generation or maintenance of heterochromatic domains.

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↗