β-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates

Continuous taste bud cell renewal is essential to maintain taste function in adults; however, the molecular mechanisms that regulate taste cell turnover are unknown. Using inducible Cre-lox technology, we show that activation of β-catenin signaling in multipotent lingual epithelial progenitors outside of taste buds diverts daughter cells from a general epithelial to a taste bud fate. Moreover, while taste buds comprise 3 morphological types, β-catenin activation drives overproduction of primarily glial-like Type I taste cells in both anterior fungiform (FF) and posterior circumvallate (CV) taste buds, with a small increase in Type II receptor cells for sweet, bitter and umami, but does not alter Type III sour detector cells. Beta-catenin activation in post-mitotic taste bud precursors likewise regulates cell differentiation; forced activation of β-catenin in these Shh⁺ cells promotes Type I cell fate in both FF and CV taste buds, but likely does so non-cell autonomously. Our data are consistent with a model where β-catenin signaling levels within lingual epithelial progenitors dictate cell fate prior to or during entry of new cells into taste buds; high signaling induces Type I cells, intermediate levels drive Type II cell differentiation, while low levels may drive differentiation of Type III cells.     

Coccinellid interactions mediated by vegetation heterogeneity

Environmental heterogeneity can have profound effects on agroecosystem function and it is important for improving ecosystem services such as biological control. Promoting system diversity via non‐crop plants is one method for increasing habitat heterogeneity within farmscapes. Non‐crop plants provide access to refuges and alternative food resources provide multiple benefits to enhance populations of arthropod predators. In this study, we examined the effects of small‐scale spatial structure on life‐stage specific interactions between the native coccinellid, Hippodamia convergensGuérin‐Méneville, and the exotic Harmonia axyridis (Pallas) (both Coleoptera: Coccinellidae), which overlap in spatial distribution in many crop systems. Squash [Cucurbita pepo L. (Cucurbitaceae)] and non‐crop mugwort [Artemisia vulgaris L. (Asteraceae)] plants with and without aphids were used as a model of spatial heterogeneity in micro‐ and mesocosm experiments. In response to factorial treatment combinations, we evaluated oviposition behavior, egg predation, larval survival, and larval predator‐prey and predator‐predator interactions. Adult H. convergens displayed higher foraging activity on aphids when exposed to complex habitats containing a non‐crop plant. In the presence of the exotic coccinellid, H. convergens preferred to deposit eggs on the non‐crop plant. Furthermore, a combination of spatial heterogeneity and prey availability reduced larval intraguild predation and cannibalism, and improved reproductive output of H. convergens by reducing intra‐ and interspecific egg predation. Our results provide evidence that life‐stage‐specific intraguild interactions are mediated by access to non‐crop plants. Thus, the introduction or maintenance of non‐crop plants has the potential to enhance coexistence of multiple natural enemies and improve top‐down control of pests.     

Deimination of human filaggrin-2 promotes its proteolysis by calpain 1

Filaggrin-2 (FLG2), a member of the S100-fused type protein family, shares numerous features with filaggrin (FLG), a key protein implicated in the epidermal barrier functions. Both display a related structural organization, an identical pattern of expression and localization in human epidermis, and proteolytic processing of a large precursor. Here, we tested whether FLG2 was a substrate of calpain 1, a calcium-dependent protease directly involved in FLG catabolism. In addition, deimination being critical for FLG degradation, we analyzed whether FLG2 deimination interfered with its proteolytic processing. With this aim, we first produced a recombinant form of FLG2 corresponding to subunits B7 to B10 fused to a COOH-terminal His tag. Incubation with calpain 1 in the presence of calcium induced a rapid degradation of the recombinant protein and the production of several peptides, as shown by Coomassie Blue-stained gels and Western blotting with anti-FLG2 or anti-His antibodies. MALDI-TOF mass spectrometry confirmed this result and further evidenced the production of non-immunoreactive smaller peptides. The degradation was not observed when a calpain 1-specific inhibitor was added. The calpain cleavage sites identified by Edman degradation were regularly present in the B-type repeats of FLG2. Moreover, immunohistochemical analysis of normal human skin revealed colocalization of FLG2 and calpain 1 in the upper epidermis. Finally, the FLG2 deiminated by human peptidylarginine deiminases was shown to be more susceptible to calpain 1 than the unmodified protein. Altogether, these data demonstrate that calpain 1 is essential for the proteolytic processing of FLG2 and that deimination accelerates this process.     

Lack of Genetic Structure and Female-Specific Effect of Dispersal Barriers in a Rabies Vector,the Striped Skunk (Mephitis mephitis)

Evaluating the permeability of potential barriers to movement, dispersal and gene exchanges can help describe spreading patterns of wildlife diseases. Here, we used landscape genetics methods to assess the genetic structure of the striped skunk (Mephitis mephitis), which is a frequent vector of rabies, a lethal zoonosis of great concern for public health. Our main objective was to identify landscape elements shaping the genetic structure of this species in Southern Québec, Canada, in an area where the raccoon rabies variant has been detected. We hypothesised that geographic distance and landscape barriers, such as highways and major rivers, would modulate genetic structure. We genotyped a total of 289 individuals sampled across a large area (22,000 km²) at nice microsatellite loci. Genetic structure analyses identified a single genetic cluster in the study area. Major rivers and highways, however, influenced the genetic relatedness among sampled individuals. Sex-specific analyses revealed that rivers significantly limited dispersal only for females while highways only had marginal effects. Rivers and highways did not significantly affect male dispersal. These results support the contention that female skunks are more philopatric than males. Overall, our results suggest that the effects of major rivers and highways on dispersal are sex-specific and rather weak and are thus unlikely to prevent the spread of rabies within and among striped skunk populations.     

Skin squamous cell carcinoma propagating cells increase with tumour progression and invasiveness

Cancer stem cells have been described in various cancers including squamous tumours of the skin by their ability to reform secondary tumours upon transplantation into immunodeficient mice. Here, we used transplantation of limiting dilution of different populations of FACS‐isolated tumour cells from four distinct mouse models of squamous skin tumours to investigate the frequency of tumour propagating cells (TPCs) at different stages of tumour progression. We found that benign papillomas, despite growing rapidly in vivo and being clonogenic in vitro, reformed secondary tumours upon transplantation at very low frequency and only when tumour cells were co‐transplanted together with tumour‐associated fibroblasts or endothelial cells. In two models of skin squamous cell carcinoma (SCC), TPCs increased with tumour invasiveness. Interestingly, the frequency of TPCs increased in CD34^HI but not in CD34^LO SCC cells with serial transplantations, while the two populations initially gave rise to secondary tumours with the same frequency. Our results illustrate the progressive increase of squamous skin TPCs with tumour progression and invasiveness and reveal that serial transplantation may be required to define the long‐term renewal potential of TPCs.     

The setae of parasitic Liphyra brassolis butterfly larvae form a flexible armour for resisting attack by their ant hosts (Lycaenidae: Lepidoptera)

Caterpillars of the lycaenid butterfly, Liphyra brassolis, live inside the nests of arboreal weaver ants, Oecophylla smaragdina, and eat their brood. Observations of mature larvae suggest that they are impervious to relentless ant molestation, yet they lack sclerotized cuticular plates. We document a novel form of integumental defence that imparts protection from ant attack whilst maintaining the flexibility necessary to walk with a hydraulic skeleton. Analysis of the trunk integument and cuticular structures of early and late instars of L. brassolis using light microscopy, scanning electron microscopy, and histology revealed three new setae types (disc, clavate, and lanceolate), as well as three new cuticular structures (pored sockets, cuticular pores, and cuticular domes). The unique cuticle is covered with lanceolate setae, which act as endocuticular struts, and overlapping scale‐like sockets, which form a hard, flexible integument. The imperfect armour of the early‐instar larvae suggests that abundant, putatively secretory pores are likely to be homologous to pore cupola organs (PCOs) found in other lycaenid larvae and thus may exude semiochemicals to allay ant aggression. The importance of these pores presumably wanes as structural (setal) cuticular defenses are reinforced in later instars, when adult ants have been observed attacking caterpillars to no avail. The caterpillar's antennae are unusual and seem to be involved in manipulating ant larvae into the caterpillar's mouth. Behavioural observations indicate that the dexterity of these structures is associated with eating ants (myrmecophagy).