Biology subjects

Pitsouli, C.

Publications and source records attributed to Pitsouli, C..

3 recordsLinked to original sources

bioRxiv2021

Remodeling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis

The Drosophila tracheal system, as the functional equivalent of mammalian blood vessels, responds to hypoxia and transports oxygen throughout the body. Although the signaling pathways involved in tracheal development and the hypoxic response are well-studied, how adult tracheae interact with their target tissues is largely unknown. Here we show that the tracheae that serve the adult intestine are dynamic and respond to enteric infection, oxidative agents, and the development of gut tumors with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated midgut regeneration and sufficient to drive ISC proliferation in the absence of damage. Gut damage or tumors induce Hif-1/Sima, which, in turn, stimulates tracheole branching via the FGF(Brachless/Bnl)/FGFR(Breathless/Btl) signaling cascade. Bnl/Btl signaling is required both in the intestinal epithelium and the tracheal system for efficient damage-induced tracheal remodeling and ISC proliferation. We show that chemical or Pseudomonas-generated ROS directly affect the trachea and are necessary for branching and intestinal regeneration. Similarly, tracheole branching and the resulting increase in oxygen supply are essential for tumor growth in the midgut. Thus, we have identified a novel mechanism of visceral tracheal-intestinal tissue communication, whereby oxidative damage and tumors induce neo-tracheogenesis in adult Drosophila. This process is reminiscent of cancer-induced neo-angiogenesis in mammals.

cell biology↗

bioRxiv2019

Intertwined trade-offs coordinate Drosophila midgut mitosis vs. endoreplication and host defense vs. dysplasia

Inflammatory signaling supports host defense against infection, not only through immune cells, but also via regeneration of damaged tissue. Heightened regeneration, nevertheless, predisposes for all types of cancer and thus a trade-off exists between regeneration capacity and long-term tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative inflammatory signaling in stem cell mitosis of the adult Drosophila midgut at the baseline and the infected state and its impact on intestinal host defense to infection and stem cell-mediated dysplasia. Through a quantitative genetics screen we find that stem cell mitosis is positively linked with the expression of eiger, Delta, upd3 and vein in the midgut, as well as with dysplasia and host defense, but negatively with enterocyte endoreplication. We provide evidence that intertwined trade-offs fine-tune midgut homeostasis, according to which stem cell mitosis through cyclin E in stem cells promotes the optimal host defense to infection, unless dysplasia ensues. However, cyclin E in enteroblasts promotes enterocyte endoreplication and counterbalances stem cell mitosis and dysplasia, providing an alternative but less efficient mechanism to support host defense.

cell biology↗

bioRxiv2018

Unpredictable effects of the genetic background of transgenic lines in physiological quantitative traits

Most physiology, fitness and disease phenotypes are considered complex traits since they exhibit continuous variation in natural populations. The use of homozygous inbred strains allows the assessment of the impact of genetic composition on complex phenotypes. Nevertheless, to understand gene function, we often combine transgenic lines to assess the phenotype of interest in a heterozygous state. Here, using inbred wild-type Drosophila strains, we assessed the phenotypic variation of six physiology and fitness traits: female fecundity, survival and intestinal mitosis upon oral infection, defecation rate and fecal pH upon oral infection, and terminal tracheal cell branching in hypoxia. Indeed, we found continuous variation in all traits tested. To estimate the extent to which small genetic background differences affected these traits, we assessed the effects of commonly used Drosophila UAS-RNAi transgenic strains and their backcrossed isogenized counterparts in the same assays. We tested 20 non-isogenic strains (10 KK and 10 GD) from the Vienna Drosophila Resource Center and their isogenic counterparts without Gal4 induction and found that the different phenotypes were variably sensitive to the genetic background. For example, survival upon infection and female fecundity exhibited differences in 50% and 40% of the tested isogenic vs. non-isogenic pairs, respectively, whereas all other phenotypes were affected in only 10-25% of the cases. We also observed that the genetic background affects Gal4 transgenes unpredictably. Thus, depending on the trait of interest, the genetic background of commonly used transgenic strains needs to be considered carefully during experimentation.

genetics↗