Cells and organisms follow aligned structures in their environment, a process that can generate persistent migration paths. Kinetic transport equations are a popular modelling tool for describing biological movements at the mesoscopic level, yet their formulations usually assume a constant turning rate. Here we relax this simplification, extending to include a turning rate that varies according to the anisotropy of a heterogeneous environment. We extend known methods of parabolic and hyperbolic scaling and apply the results to cell movement on micropatterned domains. We show that inclusion of orientation dependence in the turning rate can lead to persistence of motion in an otherwise fully symmetric environment and generate enhanced diffusion in structured domains.

To investigate the roles of lncRNA deleted in lymphocytic leukaemia 1 (DLEU1) on migration and invasion of human trophoblast cells. Human chorionic trophoblast cell line HTR8/SVneo was cultured and transfected using lncRNA DLEU1 small interfering RNA. Real-time quantitative polymerase chain reaction was used to detect lncRNA DLEU1 expression. The activity of migration regulatory protein CDC42 was detected by western blot. The downstream miRNA targets of lncRNA and mRNAs targeted by corresponding miRNAs were respectively predicted using bioinformatics analyses. Compared with the control group, the expression of lncRNA DLEU1 in the small interfering RNA group was significantly decreased (P < 0.05). There was no significant change in cell proliferation capacity for transfected cells (lncRNA DLEU1 siRNA-1, P = 0.537; lncRNA DLEU1 siRNA-2, P = 0.384), but cell migration (lncRNA DLEU1 siRNA-1, P = 0.025; lncRNA DLEU1 siRNA-2, P = 0.019) and invasion (lncRNA DLEU1 siRNA-1, P = 0.0327; lncRNA DLEU1 siRNA-2, P = 0.021) was significantly reduced. CDC42 activity in the lncRNA DLEU1 knockdown group decreased and the phosphorylation of cofilin increased. Therefore, downregulation of lncRNA DLEU1 suppressed the migration and invasion of human trophoblast cells.

The mammalian oviduct plays a pivotal role in the success of early reproductive events. The urokinase plasminogen activator system (uPAS) is present in the bovine oviduct and is involved in extracellular matrix remodelling through plasmin generation. This system can be regulated by several members of the vascular endothelial growth factors (VEGF) and their receptors. In this study, the VEGF-D effect on the regulation of uPAS was evaluated. First, RT-polymerase chain reaction (PCR) analyses were used to evidence the expression of VEGF-D and its receptors in oviductal epithelial cells (BOEC). VEGF-D, VEGFR2 and VEGFR3 transcripts were found in ex vivo and in vitro BOEC, while only VEGFR2 mRNA was present after in vitro conditions. VEGF-D showed a regulatory effect on uPAS gene expression in a dose-dependent manner, inducing an increase in the expression of both uPA and its receptor (uPAR) at 24 h post-induction and decreases in the expression of its inhibitor (PAI-1). In addition, the regulation of cell migration induced by VEGF-D and uPA in BOEC monolayer cultures was analyzed. The wound areas of monolayer cultures incubated with VEGF-D 10 ng/ml or uPA 10 nM were modified and significant differences were found at 24 h for both stimulations. These results indicated that uPAS and VEGF-D systems can modify the arrangement of the bovine oviductal epithelium and contribute to the correct maintenance of the oviductal microenvironment.

Recent developments in quantitative image analysis allow us to interrogate confocal microscopy images to answer biological questions. Clumped and layered cell nuclei and cytoplasm in confocal images challenges the ability to identify subcellular compartments. To date, there is no perfect image analysis method to identify cytoskeletal changes in confocal images. Here, we present a multidisciplinary study where an image analysis model was developed to allow quantitative measurements of changes in the cytoskeleton of cells with different maspin exposure. Maspin, a noninhibitory serpin influences cell migration, adhesion, invasion, proliferation, and apoptosis in ways that are consistent with its identification as a tumor metastasis suppressor. Using different cell types, we tested the hypothesis that reduction in cell migration by maspin would be reflected in the architecture of the actin cytoskeleton. A hybrid marker-controlled watershed segmentation technique was used to segment the nuclei, cytoplasm, and ruffling regions before measuring cytoskeletal changes. This was informed by immunohistochemical staining of cells transfected stably or transiently with maspin proteins, or with added bioactive peptides or protein. Image analysis results showed that the effects of maspin were mirrored by effects on cell architecture, in a way that could be described quantitatively.

During heart valve development, epithelial–mesenchymal transformation (EMT) is a key process for valve formation. EMT leads to the generation of mesenchymal cells that will eventually become the interstitial cells (fibroblasts) of the mature valve. During EMT, cell architecture and motility change markedly; significant changes are also observed in various signaling pathways. Here we systematically examined the expression, localization, and function of zyxin, a focal adhesion protein, in EMT during atrioventricular (AV) valve morphogenesis. Expression and localization studies showed that zyxin was expressed in the AV canal region during crucial stages of valve development. An in vitro 3D collagen gel culture system was used to determine zyxin function either after siRNA gene knockdown or after overexpression. Our studies revealed that zyxin overexpression inhibited endocardial cell migration and cell differentiation and also led to a decrease in the number of migrating mesenchymal cells. Moreover, correlative cytoskeletal changes were apparent in response to both overexpression and knockdown treatments. Thus, zyxin appears to play a role as a regulator of cell migration and differentiation during EMT in chicken AV valve formation.

This paper is concerned with a non-homogeneous in space and non-local in time random walk model for anomalous subdiffusive transport of cells. Starting with a Markov model involving a structured probability density function, we derive the non-local in time master equation and fractional equation for the probability of cell position. We derive the fractional Fokker-Planck equation for the density of cells and apply this equation to the anomalous chemotaxis problem. We show the structural instability of fractional subdiffusive equation with respect to the partial variations of anomalous exponent. We find the criteria under which the anomalous aggregation of cells takes place in the semi-infinite domain.

Neospora caninum is an intracellular parasite that poses a unique ability to infect a variety of cell types by causing host cell migration. Although previous studies demonstrated that parasite-derived proteins could trigger host cell migration, the related molecules have yet to be determined. Our study aimed to investigate the relationship between Neospora-derived molecules and host cell migration using recombinant protein of N. caninum cyclophilin (NcCyp). Indirect fluorescent antibody test revealed that NcCyp was expressed in the tachyzoite cytosol. Furthermore, NcCyp release from extracellular parasites was detected by sandwich enzyme-linked immunosorbent assay in a time-dependent manner. Recombinant NcCyp caused the cysteine–cysteine chemokine receptor 5-dependent migration of murine and bovine cells. Furthermore, immunohistochemistry indicated that NcCyp was consistently detected in tachyzoites distributed within or around the brain lesions. In conclusion, N. caninum-derived cyclophilin appears to contribute to host cell migration, thereby maintaining parasite/host interactions.

Gliomas are highly invasive brain tumors that exhibit high and spatially heterogeneouscell proliferation and motility rates. The interplay of proliferation and migrationdynamics plays an important role in the invasion of these malignant tumors. We analyze theregulation of proliferation and migration processes with a lattice-gas cellular automaton(LGCA). We study and characterize the influence of the migration/proliferation dichotomy(also known as the “GO-or-Grow" mechanism) on avascular glioma invasion, in terms ofinvasion speed and width of the infiltration zone. We show that the invasive behavior ofthe (macroscopic) tumor colony is a highly complex phenomenon that cannot be extrapolatedby the sole knowledge of the (microscopic) individual cell phenotype.

The aim of this study was to describe and analyze the regulation and spatio-temporaldynamics of melanocyte migration in vitro and its coupling to celldivision and interaction with the matrix. The melanocyte lineage is particularlyinteresting because it is involved in both embryonic development andoncogenesis/metastasis (melanoma). Biological experiments were performed on two melanocytecell lines established from wild-type and β-catenin-transgenic mice(bcat*). The multi-functional β-catenin molecule is known to be able toregulate the transcription of various genes involved in cell proliferation and migration,particularly in the melanocyte lineage. We also investigated fibronectin, anextra-cellular matrix protein that binds integrins, thereby providing adhesion points forcells and encouraging migration. As the migration of individual cells were followed,automated methods were required for processing the large amount of data generated by thetime-lapse video-microscopy. A model-based approach for automated cell tracking wasevaluated on a sample by comparison with manual tracking. This method was found reliablein studying overall cell behaviour. Its application to all the observed sequences providedinsight into the factors affecting melanocyte migration in vitro:melanocytes of mutated form of β-catenin showed higher division rates andno contact inhibition of growth was induced by the resulting increase in cell density.However, cell density limited the amplitude of cell displacements, although their motilitywas less affected. The high fibronectin concentration bound to substratum promoted cellmigration and motility, the effect being more intense for wild-type cells than for cellswith β-catenin over-expression. During the division process, cellmigration speed increased rapidly then decreased slowly. Analyses of such data is expectedto lead both to biological answers and to a framework for a better modeling processes inthe future.

Neural progenitor cells that express the NG2 proteoglycan are present in different regions of the adult mammalian brain where they display distinct morphologies and proliferative rates. In the developing postnatal and adult mouse, NG2+ cells represent a major cell population of the subventricular zone (SVZ). NG2+ cells divide in the anterior and lateral region of the SVZ, and are stimulated to proliferate and migrate out of the SVZ by focal demyelination of the corpus callosum (CC). Many NG2+ cells are labeled by GFP-retrovirus injection into the adult SVZ, demonstrating that NG2+ cells actively proliferate under physiological conditions and after demyelination. Under normal physiological conditions and after focal demyelination, proliferation of NG2+ cells is significantly attenuated in wa2 mice, which are characterized by reduced signaling of the epidermal growth factor receptor (EGFR). This results in reduced SVZ-to-lesion migration of NG2+ cells and oligodendrogenesis in the lesion. Expression of vascular endothelial growth factor (VEGF) and EGFR ligands, such as heparin binding-EGF and transforming growth factor α, is upregulated in the SVZ after focal demyelination of the CC. EGF-induced oligodendrogenesis and myelin protein expression in wild-type SVZ cells in culture are significantly attenuated in wa2 SVZ cells. Our results demonstrate that the response of NG2+ cells in the SVZ and their subsequent differentiation in CC after focal demyelination depend on EGFR signaling.

Many cells, including neuronal and glial progenitor cells, stem cells and microglial cells, have the capacity to move through the extracellular spaces of the developing and mature brain. This is particularly pronounced in astrocyte-derived tumors, gliomas, which diffusely infiltrate the normal brain. Although a significant body of literature exists regarding signals that are involved in the guidance of cells and their processes, little attention has been paid to cell-shape and cell-volume changes of migratory cells. However, extracellular spaces in the brain are very narrow and represent a major obstacle that requires cells to dynamically regulate their volume. Recent studies in glioma cells show that this involves the secretion of Cl− and K+ with water. Pharmacological inhibition of Cl− channels impairs their ability to migrate and limits tumor progression in experimental tumor models. One Cl−-channel inhibitor, chlorotoxin, is currently in Phase II clinical trials to treat malignant glioma. This article reviews our current knowledge of cell-volume changes and the role of ion channels during the migration of glioma cells. It also discusses evidence that supports the importance of channel-mediated cell-volume changes in the migration of immature neurons and progenitor cells during development. New unpublished data is presented, which demonstrates that Cl− and K+ channels involved in cell shrinkage localize to lipid-raft domains on the invadipodia of glioma cells and that their presence might be regulated by trafficking of these proteins in and out of lipid rafts.

The adhesion of cells to their surrounding extracellular matrix has vital roles in embryonic development, inflammatory responses, wound healing and adult tissue homeostasis. Cells attach to extracellular matrix by specific cell-surface receptors, of which the integrins and transmembrane proteoglycans are major representatives. The engagement of adhesion receptors triggers assembly of functional matrix contacts, in which bound matrix components, adhesion receptors and associated intracellular cytoskeletal and signalling molecules form large, localised multiprotein complexes. This review discusses the functional categories of matrix contacts, examples of the biological roles of matrix contacts in normal physiology, and examples of the ways in which abnormalities of matrix contacts are associated with major human diseases.

Viruses replicate inside host cells, where they use host biochemical and structural components to facilitate the production of new virus particles. As a consequence of co-evolution with their hosts, viruses have acquired host genes and genetic mutations that confer dominance over normal cell function. Research on virus–cell interactions has focused on the identification of mechanisms of virus dominance in order to develop therapeutic strategies for preventing productive infection. Although such research remains an essential part of molecular virology, viruses are also important genetic tools that can be used to analyse cell function. Because virus genomes contain genetic information, some of which was derived from host cells, it is possible that the analyses of virus–host interactions might lead to the identification of functionally dominant virus genes and novel eukaryotic counterparts. In this article, we have described how transforming and non-transforming viruses can control cell motility (cell migration or membrane projection), and explained how the analysis of virus cytopathic effects (CPEs) led to the identification of a novel family of cellular genes that regulate diverse aspects of cell motility.

These studies in fetal monkeys and ferrets show that the two fundamental types of thalamic GABA neuron populate the thalamus during widely separated developmental epochs. Those of the ventral thalamus (VT) and epithalamus (ET) appear very early in conjunction with the GABA cells of the substantia nigra, globus pallidus, and pretectum (PT). GABA neurons intrinsic to the dorsal thalamus (DT) appear later, long after proliferative activity has ceased in the wall of the third ventricle, after dorsal thalamic nuclei have differentiated and at the same time as principal neurons are acquiring a glutamatergic phenotype. The exact origins of the two waves of GABA cells are uncertain but some appear to arrive from extrinsic sources that include the ganglionic eminence (GE) of the basal forebrain.

Development of the neural crest involves a remarkable feat of coordinated cell migration in which cells detach from the neural tube, take varying routes of migration through the embryonic tissues and then differentiate at the end of their journey to participate in the formation of a number of organ systems. In general, neural crest cells appear to migrate without the guidance of long-range physical or chemical cues, but rather they respond to heterogeneity in the extracellular matrix that forms their migration substrate. Molecules such as fibronectin and laminin act as permissive substrate components, encouraging neural crest cell attachment and spreading, whereas chondroitin sulphate proteoglycans are nonpermissive for migration. A balance between permissive and nonpermissive substrate components seems to be necessary to ensure successful migration, as indicated by a number of studies in mouse mutant systems where nonpermissive molecules are over-expressed, leading to inhibition of neural crest migration. The neural crest expresses cell surface receptors that permit interaction with the extracellular matrix and may also modify the matrix by secretion of proteases. Thus the principles that govern the complex migration of neural crest cells are beginning to emerge.