Biology subjects

Bossen, J.

Publications and source records attributed to Bossen, J..

5 recordsLinked to original sources

bioRxiv2026

Preconception e-nicotine impairs airway development and progenitor proliferation across generations in Drosophila Melanogaster

Electronic nicotine delivery devices are increasingly used worldwide, raising concern about the potential effects of nicotine exposure during fetal and early postnatal development. However, evidence regarding the effects of vaping during pregnancy remains limited, and the consequences of exposure before conception are largely unknown. Here, we investigated whether maternal nicotine vaping prior to conception alters airway development using the fruit fly Drosophila melanogaster. Offspring of nicotine-exposed mothers exhibited abnormal airway architecture, epithelial remodelling, and impaired terminal branching. These defects were accompanied by reduced proliferation of airway progenitor cells without increased apoptosis, resulting in decreased hypoxia tolerance, altered activity patterns, and reduced lifespan. Transcriptomic and functional analyses revealed suppression of innate immune signalling mediated by nuclear factor kappa-B (NF-{kappa}B). Notably, knockdown of its regulator Relish reproduced key phenotypes. Developmental abnormalities persisted across generations, with their severity progressively declining. Together, these findings identify maternal preconception nicotine exposure as a previously unrecognized determinant of airway development and provide insight into early origins of chronic airway disease. TeaserPreconception e-nicotine exposure shapes airway development, structural and physiological abnormalities across generations in Drosophila.

Developmental Biology↗

bioRxiv2025

JNK integrates immune and stress signals to balance apoptosis and proliferation in airway progenitors

Chronic inflammation disrupts epithelial regeneration, yet how immune signaling reprograms progenitor fate remains unclear. Using the Drosophila airway as a model of epithelial remodeling, we identify the c-Jun N-terminal kinase (JNK) pathway as a central integrator of immune and stress cues that balances apoptosis and compensatory proliferation in airway progenitors. Persistent activation of the innate immune IMD pathway induces simultaneous cell death and proliferation through a non-canonical route that bypasses NF-{kappa}B/Relish and instead engages JNK. Downstream, distinct transcriptional modules orchestrate these divergent fates: Foxo and AP-1 drive apoptosis, whereas the ETS factor Ets21C mediates proliferation. Genetic inhibition of JNK or its effectors restores progenitor homeostasis, while constitutive activation recapitulates inflammation-induced tissue remodeling. These responses are cell-autonomous, revealing that airway progenitors actively interpret immune and stress signals to determine their fate. Collectively, our findings uncover a modular signaling architecture that links inflammation to regeneration and highlight conserved JNK-dependent transcriptional programs as potential therapeutic targets to prevent progenitor exhaustion in chronic airway disease.

cell biology↗

bioRxiv2023

A mitochondrial sirtuin shapes the intestinal microbiota by controlling lysozyme expression

Sirtuins act as cellular sensors in the gut that control a substantial change in gut properties in response to environmental changes. Here we show that the only mitochondrial sirtuin of Drosophila, dSirt4, is strongly up-regulated by a protein-reduced diet. Flies with a dSirt4 defect show strong changes in the protein pattern and physiological properties of their intestine. One of the most notable effects was the strong induction of lysozyme gene expression in the intestine, which also translates into enhanced lysozyme activity. This effect was cell autonomous, as it was also observed in flies with dsirt4 was exclusively silenced in enterocytes of the intestine. Although this strongly increased lysozyme expression, it did not reduce total bacterial load in the intestine, but rather changed the composition of the microbiota by reducing the number of gram-positive bacteria. This effect on microbiota composition can be attributed to the dSirt4-dependent lysozyme expression, as it was absent in a lysozyme-deficient background. dSirt4 deficiency in enterocytes reduced lifespan of flies, which was also observed in those flies experiencing ectopic lysozyme overexpression in enterocytes. This implies that strong lysozyme expression leads to a dysbiotic state associated with reduced lifespan.

cell biology↗

bioRxiv2023

Recurrent phases of strict protein limitation inhibit tumor growth and restore lifespan in a Drosophila intestinal cancer model

Diets that restrict caloric or protein intake offer a variety of benefits, including decreasing the incidence of cancer. However, whether such diets pose a substantial therapeutic benefit as auxiliary cancer treatments remains unclear. We determined the effects of severe protein depletion on tumorigenesis in a Drosophila melanogaster intestinal tumor model, using a human RAF gain-of-function allele. Severe and continuous protein restriction significantly reduced tumor growth but resulted in premature death. Therefore, we developed a diet in which short periods of severe protein restriction alternated cyclically with periods of complete feeding. This nutritional regime reduced tumor mass, restored gut functionality, and normalized the lifespan of oncogene-expressing flies to the levels observed in healthy control flies. Furthermore, this diet reduced the chemotherapy-induced stem cell activity associated with tumor recurrence. Transcriptome analysis revealed long-lasting changes in the expression of key genes involved in multiple major developmental signaling pathways. Overall, the data suggest that recurrent severe protein depletion effectively mimics the health benefits of continuous protein restriction, without undesired nutritional shortcomings. This provides seminal insights into the mechanisms of the transcriptomic memory effect required to maintain the positive effects of protein restriction throughout the phases of a full diet.

cancer biology↗

bioRxiv2020

Balanced JAK/STAT signaling is critical to maintain the functional and structural integrity of the Drosophila respiratory epithelium

Signaling mediated by the Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is critical for maintaining cellular and functional homeostasis in the lung. Thus, chronically activated JAK/STAT signaling is causally associated with lung diseases such as lung cancer, asthma, and chronic obstructive pulmonary disease. To elucidate the molecular processes that transform increased JAK/STAT signaling in airway epithelial cells into the known pathological states, we used a highly simplified model system, the fruit fly Drosophila melanogaster. Here, the JAK/STAT pathway is permanently active in almost all airway cells and responds to airborne stressors with increased activity. Silencing of this signaling pathway in epithelial cells resulted in apoptosis. Since the above-mentioned lung diseases are commonly associated with increased JAK/STAT signaling, we assessed this by its ectopic activation in the respiratory epithelium of Drosophila. This intervention triggered cell-autonomous structural changes in epithelial cells. These structural changes included phenotypes associated with asthma, namely, thickening of the epithelium, substantial narrowing of the air-conducting space, and impairment of the secretory epicuticular structure of the tracheae. Pharmacological manipulation of JAK/STAT signaling reversed this pathological phenotype. Transcriptomic analyses revealed that several biological processes were affected, which is consistent with the impairment of junction protein trafficking also observed in this study. These results indicate that balanced JAK/STAT signaling is essential for the functionality of the respiratory epithelium and, by extension, the entire organ. In contrast, chronic overactivation of this signaling leads to massive structural changes that are closely associated with pathologies typical of chronic inflammatory lung diseases. HighlightsO_LIJAK/STAT signaling is active in the entire Drosophila respiratory system in all developmental stages. C_LIO_LIThe signaling pathway is indispensable for the survival of the tracheal cell. C_LIO_LIOveractivation of the signaling has significant effects on tracheal development and also displays a human disease-associated phenotype in Drosophila trachea. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/160929v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1f82913org.highwire.dtl.DTLVardef@150a79corg.highwire.dtl.DTLVardef@2c1130org.highwire.dtl.DTLVardef@11c7cf8_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗