Fisher Waves and Front Roughening in a Two-Species Invasion Model with Preemptive Competition

We study front propagation when an invading species competes with a resident; we assume nearest-neighbor preemptive competition for resources in an individual-based, two-dimensional lattice model. The asymptotic front velocity exhibits power-law dependence on the difference between the two species' clonal propagation rates (key ecological parameters). The mean-field approximation behaves similarly, but the power law's exponent slightly differs from the individual-based model's result. We also study roughening of the front, using the framework of non-equilibrium interface growth. Our analysis indicates that initially flat, linear invading fronts exhibit Kardar-Parisi-Zhang (KPZ) roughening in one transverse dimension. Further, this finding implies, and is also confirmed by simulations, that the temporal correction to the asymptotic front velocity is of ${\cal O}(t^{-2/3})$.Comment: 8 pages, 5 figures; Papers on related work can be found at http://www.rpi.edu/~korniss/Researc

Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia

Familial dysautonomia (FD) is a developmental neuropathy of the sensory and autonomous nervous systems. The IKBKAP gene, encoding the IKAP/hELP1 subunit of the RNA polymerase II Elongator complex is mutated in FD patients, leading to a tissue-specific mis-splicing of the gene and to the absence of the protein in neuronal tissues. To elucidate the function of IKAP/hELP1 in the development of neuronal cells, we have downregulated IKBKAP expression in SHSY5Y cells, a neuroblastoma cell line of a neural crest origin. We have previously shown that these cells exhibit abnormal cell adhesion when allowed to differentiate under defined culture conditions on laminin substratum. Here, we report results of a microarray expression analysis of IKAP/hELP1 downregulated cells that were grown on laminin under differentiation or non-differentiation growth conditions. It is shown that under non-differentiation growth conditions, IKAP/hELP1 downregulation affects genes important for early developmental stages of the nervous system, including cell signaling, cell adhesion and neural crest migration. IKAP/hELP1 downregulation during differentiation affects the expression of genes that play a role in late neuronal development, in axonal projection and synapse formation and function. We also show that IKAP/hELP1 deficiency affects the expression of genes involved in calcium metabolism before and after differentiation of the neuroblastoma cells. Hence, our data support IKAP/hELP1 importance in the development and function of neuronal cells and contribute to the understanding of the FD phenotype

LGR5 Is a Negative Regulator of Tumourigenicity, Antagonizes Wnt Signalling and Regulates Cell Adhesion in Colorectal Cancer Cell Lines

BACKGROUND: LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) is the most established marker for intestinal stem cells. Mouse models show that LGR5+ cells are the cells of origin of intestinal cancer, and LGR5 expression is elevated in human colorectal cancers, however very little is known about LGR5 function or its contribution to the stem cell phenotype and to colorectal cancer. PRINCIPAL FINDINGS: We have modulated the expression of LGR5 by RNAi (inhibitory RNAs) or overexpression in colorectal cancer cell lines. Paradoxically, ablation of LGR5 induces increased invasion and anchorage-independent growth, and enhances tumourigenicity in xenografts experiments. Conversely, overexpression of LGR5 augments cell adhesion, reduces clonogenicity and attenuates tumourigenicity. Expression profiling revealed enhanced wnt signalling and upregulation of EMT genes upon knockdown of LGR5, with opposite changes in LGR5 overexpressing cells. These findings suggest that LGR5 is important in restricting stem cells to their niche, and that loss of LGR5 concomitant with activated wnt signalling may contribute to the invasive phenotype of colorectal carcinomas

Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer

Modeling competition, niche, and coexistence between an invasive and a native species in a two‐species metapopulation

International audienceModeling the dynamics of competition and coexistence between species is cru-cial to predict long-term impacts of invasive species on their native congeners. However, natu-ral environments are often fragmented and variable in time and space. In such contexts,regional coexistence depends on complex interactions between competition, niche differentia-tion and stochastic colonization–extinction dynamics. Quantifying all these processes at land-scape scale has always been a challenge for ecologists. We propose a new statistical frameworkto evaluate metapopulation parameters (colonization and extinction) in a two-species systemand how they respond to environmental variables and interspecific competition. It requiresspatial surveys repeated in time, but does not assume demographic equilibrium. We apply thismodel to a long-term survey of two snails inhabiting a network of freshwater habitats in theWest Indies. We find evidence of reciprocal competition affecting colonization or extinctionrates, modulated by species-specific sensitivity to environmental variables. Simulations usingmodel estimates allow us to predict species dynamics and explore the role of various coexis-tence mechanisms described by metacommunity theory in our system. The two species are pre-dicted to stably coexist, because niche partitioning, source–sink dynamics and interspecificdifferences in extinction–colonization parameters all contribute to reduce the negative impactsof competition. However, none of these mechanisms is individually essential. Regional coexis-tence is primarily facilitated by transient co-occurrence of the two species within habitatpatches, a possibility generally not considered in theoretical metacommunity models. Ourframework is general and could be extended to guilds of several competing species