Project description:The extracellular matrix is essential for tissue formation and regeneration through the control of cellular behavior. Deregulation of extracellular matrix components is associated to disease, including neurodegeneration. After peripheral nerve injury, Schwann cells guide regrowing axons to their targets. These glial cells migrate collectively and provide an extracellular environment to enable neural repair. How this occurs remains poorly understood. Here, we show that Sox2 controls fibronectin fibrillogenesis in Schwann cells to provide a highly oriented extracellular matrix, which supports their rapid collective migration with a continuous cellular flow. Sox2 directly activates fibronectin expression in Schwann cells, leading to an increase in fibrillogenesis and cellular huddling. Accordingly, loss of fibrillogenesis leads to glial disassembly and disorganized axon regrowth. In vivo, 7 days post nerve injury, we found that pro-regenerative Schwann cells co-express Sox2 and the EIIIA-containing fibronectin splicing isoform. This mechanism is conserved in mammals, including humans, but absent in zebrafish. Taken together, our results demonstrate that Sox2 directly controls fibrillogenesis and provide a novel mechanism for the modification of the environmental architecture by glial cells during neuronal repair.
Project description:We investigated two microenvironmental factors, tumor-intrinsic hypoxia, and tumor-secreted factors (secretome) as triggers of collective migration using a three-dimensional (3D) discrete-sized microtumor models that recapitulate hallmarks of Ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition. These two factors induced two distinct modes of collective migration: directional and radial migration in the 3D microtumors generated from the same breast cancer cell line model, T47D. Without external stimulus, large (>500µm) T47D microtumors exhibited tumor-intrinsic hypoxia and directional collective migration while small (<150 µm), non-hypoxic microtumors exhibited radial collective migration only when exposed to secretome of large microtumors. To investigate the differences in the underlying mechanism present between hypoxia- and secretome-induced directional versus radial migration modes, we performed differential gene expression analysis of hypoxia- and secretome-induced migratory microtumors vs. non-hypoxic, non-migratory small microtumors as controls. We used microarrays to detail the global programme of gene expression profiling to study tumor intrinsic hypoxia induced directional migration and secretom induced radial migrartion in large 600µm microtumors with small 150μm microtumors as controls in three dimensional (3D) breast microtumor model
Project description:Few studies have assessed the patterns of parasite populations of rodents over a longitudinal gradient in Chile. In this work, the gastrointestinal helminthic fauna of invasive rodents in Chile was examined to assess the association between their presence/absence and abundance with latitude, host sex, and host body condition, and to assess the coexistence and correlation of the abundance between parasite species. Rodents were obtained from 20 localities between 33 and 43°S. Helminths were extracted from the gastrointestinal tract and identified morphologically. Overall, 13 helminth taxa were obtained. The most frequently identified parasite species was Heterakis spumosa, and the most abundant was Syphacia muris, while Physaloptera sp. was the most widely distributed. No locality presented with a coexistence that was different from that expected by chance, while the abundance of five helminthic species correlated with the abundance of another in at least one locality, most likely due to co-infection rather than interaction. Host sex was associated with parasite presence or abundance, and female sex-biased parasitism was notably observed in all cases. Body condition and latitude presented either a positive or negative association with the presence or abundance of parasites depending on the species. It is notable that the likely native Physaloptera sp. is widely distributed among invasive rodents. Further, gravid females were found, suggesting spillback of this species to the native fauna. The low frequency and abundance of highly zoonotic hymenolepid species suggest that rodents are of low concern regarding gastrointestinal zoonotic helminths.
Project description:Fibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular-matrix. However, force transmission is in itself dependent on fibrillogenesis, and fibronectin fibrils are found in soft embryos where high forces cannot be applied, suggesting that force cannot be the sole initiator of fibrillogenesis. Here we identify a novel nucleation step prior to force transmission, driven by fibronectin oxidation mediated by lysyl-oxidase enzyme family members. This oxidation induces fibronectin clustering that promotes early adhesion, alters cellular response to soft matrices, and enhances force transmission to the matrix. In contrast, absence of fibronectin oxidation abrogates fibrillogenesis, perturbs cell-matrix adhesion, and compromises mechanosensation. Moreover, fibronectin oxidation promotes cancer cells colony formation in soft agar as well as collective and single-cell migration. These results reveal a yet unidentified, force-independent enzyme-dependent mechanism that initiates fibronectin fibrillogenesis, establishing a critical step in cell adhesion and mechanosensing.
Project description:Fibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular-matrix. However, force transmission is in itself dependent on fibrillogenesis, and fibronectin fibrils are found in soft embryos where high forces cannot be applied, suggesting that force cannot be the sole initiator of fibrillogenesis. Here we identify a novel nucleation step prior to force transmission, driven by fibronectin oxidation mediated by lysyl-oxidase enzyme family members. This oxidation induces fibronectin clustering that promotes early adhesion, alters cellular response to soft matrices, and enhances force transmission to the matrix. In contrast, absence of fibronectin oxidation abrogates fibrillogenesis, perturbs cell-matrix adhesion, and compromises mechanosensation. Moreover, fibronectin oxidation promotes cancer cells colony formation in soft agar as well as collective and single-cell migration. These results reveal a yet unidentified, force-independent enzyme-dependent mechanism that initiates fibronectin fibrillogenesis, establishing a critical step in cell adhesion and mechanosensing.
Project description:In the context of breast cancer metastasis study, we have shown in an in vitro model of cell migration that IGDQ-exposing (IsoLeu-Gly-Asp-Glutamine type I Fibronectin motif) monolayers (SAMs) on gold sustain the adhesion of MDA-MB-231 cells by triggering Focal Adhesion Kinase by activating integrins. Such tunable scaffolds are used to mimic the extracellular environment, inducing and controlling cell migration towards an anisotropic surface. The observed migratory behavior induced by the IGDQ-bearing peptide gradient along the surface suggests the presence of cell subpopulations: “stationary” or a “migratory” phenotype. We focused on the integrins α5(β1) and (αv)β3, already known to be implicated in cell migration. To this aim, a whole proteomic analysis was performed in beta 3 integrin (ITGB3) or alpha 5 integrin (ITGA5) knock-down MDA-MB-231, in order to highlight the pathways implied into the integrin-dependent cell migration. Our results showed that i) ITGB3 depletion influenced ITGA5 mRNA expression, ii) ITGB3 and ITGA5 were both necessary for IGDQ-mediated directional single cell migration, iii) integrin (αv)β3 was activated by IGDQ fibronectin type I motif and iv) co-regulation of retrograde transport of ITGB3 by ITGA5 is potentially necessary for directional IGDQ-mediated cell migration.
Project description:Analysis of LBNF1 rat testes from controls, containing both somatic and all germ cell types and from irradiated rats in which all cells germ cells except type A spermatgogonia are eliminated. Results provide insight into distinguishing germ and somatic cell genes and identification of somatic cell genes that are upregulated after irradiation.
Project description:The Norway rat has important impacts on our life. They are amongst the most used research subjects, resulting in ground-breaking advances. At the same time, wild rats live in close association with us, leading to various adverse interactions. In face of this relevance, it is surprising how little is known about their natural behaviour. While recent laboratory studies revealed their complex social skills, little is known about their social behaviour in the wild. An integration of these different scientific approaches is crucial to understand their social life, which will enable us to design more valid research paradigms, develop more effective management strategies, and to provide better welfare standards. Hence, I first summarise the literature on their natural social behaviour. Second, I provide an overview of recent developments concerning their social cognition. Third, I illustrate why an integration of these areas would be beneficial to optimise our interactions with them.
Project description:BackgroundMurine kobuviruses (MuKV) are newly recognized picornaviruses first detected in murine rodents in the USA in 2011. Little information on MuKV epidemiology in murine rodents is available. Therefore, we conducted a survey of the prevalence and genomic characteristics of rat kobuvirus in Guangdong, China.ResultsFecal samples from 223 rats (Rattus norvegicus) were collected from Guangdong and kobuviruses were detected in 12.6% (28) of samples. Phylogenetic analysis based on partial 3D and complete VP1 sequence regions showed that rat kobuvirus obtained in this study were genetically closely related to those of rat/mouse kobuvirus reported in other geographical areas. Two near full-length rat kobuvirus genomes (MM33, GZ85) were acquired and phylogenetic analysis of these revealed that they shared very high nucleotide/amino acids identity with one another (95.4%/99.4%) and a sewage-derived sequence (86.9%/93.5% and 87.5%/93.7%, respectively). Comparison with original Aichivirus A strains, such human kobuvirus, revealed amino acid identity values of approximately 80%.ConclusionOur findings indicate that rat kobuvirus have distinctive genetic characteristics from other Aichivirus A viruses. Additionally, rat kobuvirus may spread via sewage.