Commensal Gut Bacteria Buffer the Impact of Host Genetic Variants on Drosophila Developmental Traits under Nutritional Stress.

Eukaryotic genomes encode several buffering mechanisms that robustly maintain invariant phenotypic outcome despite fluctuating environmental conditions. Here we show that the Drosophila gut-associated commensals, represented by a single facultative symbiont, Lactobacillus plantarum (LpWJL), constitutes a so far unexpected buffer that masks the contribution of the host's cryptic genetic variation (CGV) to developmental traits while the host is under nutritional stress. During chronic under-nutrition, LpWJL consistently reduces variation in different host phenotypic traits and ensures robust organ patterning during development; LpWJL also decreases genotype-dependent expression variation, particularly for development-associated genes. We further provide evidence that LpWJL buffers via reactive oxygen species (ROS) signaling whose inhibition impairs microbiota-mediated phenotypic robustness. We thus identified a hitherto unappreciated contribution of the gut facultative symbionts to host fitness that, beyond supporting growth rates and maturation timing, confers developmental robustness and phenotypic homogeneity in times of nutritional stress.

Boundary repair: Science and enterprise at the Chinese Academy of Sciences.

In the 1980s, the Chinese state pushed the Chinese Academy of Sciences (CAS) to establish businesses. Some of these businesses did not engage in any research and development (R&D), and this resulted in scientists having concerns about the boundary around the institutionalizing scientific community. When the state supported CAS's 'Knowledge Innovation' reform in the late 1990s, CAS's organizing principle became centered on a more narrowly scientific logic, which led to less reliance on business income. Regression analysis indicates that CAS-owned enterprises without R&D were more likely to be discontinued during 'Knowledge Innovation'. Moreover, businesses having no R&D were more likely to be discontinued (1) if they were making high profits and (2) if they were supervised by an institute in which Academicians had longer tenure, because these conditions heightened science-market conflict.

A New Transkingdom Dimension to NO Signaling.

Bacterial-derived metabolites profoundly influence the host's cellular and organismal physiology. Seth et al. (2019) report that via interspecies S-nitrosylation, microbiota-derived nitric oxide directly alters the host's Argonaute family protein activity, and consequently impinges on the overall post-transcriptional gene silencing program through the microRNA (miRNA) machinery.

The importance of being persistent: The first true resident gut symbiont in Drosophila.

In the animal kingdom, nutritional mutualism is a perpetual and intimate dialogue carried out between the host and its associated gut community members. This dialogue affects many aspects of the host's development and physiology. Some constituents of the animal gut microbiota can stably reside within the host for years, and such long-term persistence might be a prerequisite for these microbes to assert their beneficial impact. How long-term persistence is established and maintained is an interesting question, and several classic model organisms associated with cultivable resident strains are used to address this question. However, in Drosophila, this model has long eluded fly geneticists. In this issue of PLOS Biology, Pais and colleagues present the most rigorous and comprehensive demonstration to date that persistence and gut residency do take place in the digestive tract of Drosophila melanogaster. This natural gut isolate of Acetobacter thailandicus stably colonizes the adult fly foregut, accelerates larval maturation, and boosts host fecundity and fertility as efficiently as the known laboratory strains. The discovery of such stable association will be a boon for the Drosophila community interested in host-microbiota interaction, as it not only provides a novel model to unravel the molecular underpinnings of persistence but also opens a new arena for using Drosophila to study the implications of gut persistence in evolution and ecology.

D-Alanylation of teichoic acids contributes to Lactobacillus plantarum-mediated Drosophila growth during chronic undernutrition.

The microbial environment influences animal physiology. However, the underlying molecular mechanisms of such functional interactions are largely undefined. Previously, we showed that during chronic undernutrition, strains of Lactobacillus plantarum, a major commensal partner of Drosophila, promote host juvenile growth and maturation partly through enhanced expression of intestinal peptidases. By screening a transposon insertion library of Lactobacillus plantarum in gnotobiotic Drosophila larvae, we identify a bacterial cell-wall-modifying machinery encoded by the pbpX2-dlt operon that is critical to enhance host digestive capabilities and promote animal growth and maturation. Deletion of this operon leads to bacterial cell wall alteration with a complete loss of D-alanylation of teichoic acids. We show that L. plantarum cell walls bearing D-alanylated teichoic acids are directly sensed by Drosophila enterocytes to ensure optimal intestinal peptidase expression and activity, juvenile growth and maturation during chronic undernutrition. We thus conclude that besides peptidoglycan, teichoic acid modifications participate in the host-commensal bacteria molecular dialogue occurring in the intestine.

Studying host-microbiota mutualism in Drosophila: Harnessing the power of gnotobiotic flies.

The complex interaction between the metazoan host and its commensal gut microbiota is one of the essential features of symbiosis in the animal kingdom. As there is a burgeoning interest to decipher the molecular dialog that shapes host-microbiota mutualism, the use of gnotobiotic model organism becomes an imperative approach to unambiguously parse the specific contributions to such interaction from the microbiome. In this review, we focus on several remarkable gnotobiotic studies in Drosophila that functionally depicted how the gut microbes can alter host physiology and behavior through transcriptomic regulation, hormonal control, and diet modification. These results in concert illustrate that the gnotobiotic flies mono- or poly-associated with members of its gut microbiota deliver a versatile and powerful model that is amenable to different types of studies ranging from classic genetics to large-scale systems approaches.

The p53 control of apoptosis and proliferation: lessons from Drosophila.

The canonical role of p53 in preserving genome integrity and limiting carcinogenesis has been well established. In the presence of acute DNA-damage, oncogene deregulation and other forms of cellular stress, p53 orchestrates a myriad of pleiotropic processes to repair cellular damages and maintain homeostasis. Beside these well-studied functions of p53, recent studies in Drosophila have unraveled intriguing roles of Dmp53 in promoting cell division in apoptosis-induced proliferation, enhancing fitness and proliferation of the winner cell in cell competition and coordinating growth at the organ and organismal level in the presence of stress. In this review, we describe these new functions of Dmp53 and discuss their relevance in the context of carcinogenesis.

Cell packing influences planar cell polarity signaling.

Some epithelial cells display asymmetry along an axis orthogonal to the apical-basal axis, referred to as planar cell polarity (PCP). A Frizzled-mediated feedback loop coordinates PCP between neighboring cells, and the cadherin Fat transduces a global directional cue that orients PCP with respect to the tissue axes. The feedback loop can propagate polarity across clones of cells that lack the global directional signal, although this polarity propagation is error prone. Here, we show that, in the Drosophila wing, a combination of cell geometry and nonautonomous signaling at clone boundaries determines the correct or incorrect polarity propagation in clones that lack Fat mediated global directional information. Pattern elements, such as veins, and sporadic occurrences of irregular geometry are obstacles to polarity propagation. Hence, in the wild type, broad distribution of the global directional cue combines with a local feedback mechanism to overcome irregularities in cell packing geometry during PCP signaling.

Fidelity in planar cell polarity signalling.

The polarity of Drosophila wing hairs displays remarkable fidelity. Each of the approximately 30,000 wing epithelial cells constructs an actin-rich prehair that protrudes from its distal vertex and points distally. The distal location and orientation of the hairs is virtually error free, thus forming a nearly perfect parallel array. This process is controlled by the planar cell polarity signalling pathway. Here we show that interaction between two tiers of the planar cell polarity signalling mechanism results in the observed high fidelity. The first tier, mediated by the cadherin Fat, dictates global orientation by transducing a directional signal to individual cells. The second tier, orchestrated by the 7-pass transmembrane receptor Frizzled, aligns each cell's polarity with that of its neighbours through the action of an intercellular feedback loop, enabling polarity to propagate from cell to cell. We show that all cells need not respond correctly to the presumably subtle signal transmitted by Fat. Subsequent action of the Frizzled feedback loop is sufficient to align all the cells cooperatively. This economical system is therefore highly robust, and produces virtually error-free arrays.

A three-tiered mechanism for regulation of planar cell polarity.

Some epithelial cells are polarized along an axis orthogonal to their apical-basal axes. Recent studies in Drosophila lead to the view that three classes of signaling molecules govern the planar cell polarity (PCP) pathway. The first class, or module, functions across whole tissues, providing directional information to individual cells. The second module, apparently shared by all planar polarized tissues, and related to the canonical Wnt signaling pathway, interprets the directional signal to produce subcellular asymmetries. The third modules are tissue specific, acting to translate subcellular asymmetry into the appropriate morphological manifestations in the different cell types.