Description: Julia Kofent, Juan Zhang, and Francesca M. Spagnoli Cell fate specification depends on transcriptional activation driven by lineage-specific transcription factors as well as changes in chromatin organization. To date, the interplay between transcription factors and chromatin modifiers during development is not well understood. We focus here on the initiation of the pancreatic program from multipotent endodermal progenitors. Transcription factors that play key roles in regulating pancreatic progenitor state have been identified, but the chromatin regulators that help to establish and maintain pancreatic fate are less well known. Using a comparative approach, we identify a crucial role for the histone methyltransferase Setd7 in establishing pancreatic cell identity. We show that Setd7 is expressed in the prospective pancreatic endoderm of Xenopus and mouse embryos prior to Pdx1 induction. Importantly, we demonstrate that setd7 is sufficient and required for pancreatic cell fate specification in Xenopus . Functional and biochemical approaches in Xenopus and mouse endoderm support that Setd7 modulates methylation marks at pancreatic regulatory regions, possibly through interaction with the transcription factor Foxa2. Together, these results demonstrate that Setd7 acts as a central component of the transcription complex initiating the pancreatic program.

Description: Understanding how distinct cell types arise from multipotent progenitor cells is a major quest in stem cell biology. The liver and pancreas share many aspects of their early development and possibly originate from a common progenitor. However, how liver and pancreas cells diverge from a common endoderm progenitor population and adopt specific fates remains elusive. Using RNA sequencing (RNA-seq), we defined the molecular identity of liver and pancreas progenitors that were isolated from the mouse embryo at two time points, spanning the period when the lineage decision is made. The integration of temporal and spatial gene expression profiles unveiled mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the noncanonical Wnt pathway as a potential developmental regulator of this fate decision and capable of inducing the pancreas program in endoderm and liver cells. Our study offers an unprecedented view of gene expression programs in liver and pancreas progenitors and forms the basis for formulating lineage-reprogramming strategies to convert adult hepatic cells into pancreatic cells.

Description: Kristin M. Petzold, Heike Naumann, and Francesca M. Spagnoli The development of functional organ architecture relies on coordinated morphogenesis and growth. In the developing pancreas, the branching epithelium is organised in discrete domains, delineating one specific domain of progenitor cells at the tip of the branches. The molecular mechanisms underlying the coordinated action of branching and proliferation in organ formation are largely unknown. Here, we identify the RhoGAP protein Stard13 as an essential regulator of pancreas tissue architecture in the mammalian embryo. Conditional ablation of Stard13 expression in the pancreas disrupts epithelial morphogenesis and tip-domain organisation, resulting in hampered proliferation of tip progenitors and subsequent organ hypoplasia. Stard13 acts by regulating Rho signalling spatially and temporally during pancreas development. Our findings provide new insights into the mechanisms that shape pancreatic epithelium to create a mature organ and establish a functional link between Rho-mediated control of epithelial remodelling and organ size determination, involving reciprocal interaction of actin-MAL/SRF and MAPK signalling pathways.

Description: In the context of the COBO project (funded by EU FP 6), consequences of a fish farm activity on biogeochemistry composition and processes of bottom sediments below the fish farm cages have been evaluated. The fish farm was located in a northern fjord (Loch Creran, Scotland). The study was carried out three months after the removing of the cages. Seven cores in May and three cores in August 2006 were collected to study early diagenesis processes and to calculate benthic fluxes. Each core was extruded; pore waters were extracted and analyzed for nutrients (NH3, NO3, NO2, PO4, Si(OH)4, and TCO2), metals (Fe and Mn) and sulphates; diffusive fluxes at the sediment-water interface were calculated by applying Ficks first law. Preliminary results show sediments lying down to the fish farm were characterized by more intensive early diagenesis processes (from 2 to 4 times more than blank area). This means the fish farm produce high reactive organic matter snow that increases the reactivity of bottom sediments. Seasonal variations with increased diagenetic processes in summer were also recorded. In spring and in summer sediments both from the impacted area and the control sites were affected by strong bio-irrigation processes. Calculated benthic fluxes reflect the early diagenesis patterns with more intensive nutrient fluxes to the overlying water in the fish farm affected area and in the summer season, this suggests sediments affected by fish farm activity contribute more to eutrophication of confined coastal waters.

Description: Marine coastal ecosystems, and in particular the sedentary benthic invertebrate communities that play a critical role in regulating coastal geochemical cycles, are compromised by human-induced stresses, including overfishing, habitat destruction, climate change and pollution. However, due to the complexity, remoteness and spatio-temporal variability of this environment, the relationships between tightly coupled biological, physical and geochemical processes are poorly understood. The combination in COBO of innovative in situ measurement instruments from different disciplines with tools for the controlled simulation of various disturbance types and numerical tools for the interpretation of new forms of in situ data will significantly advance our understanding of organism-sediment interactions under dynamic coastal conditions. Integrated observations of the natural environment at high spatial and temporal resolution enable a quantitative and mechanistic understanding of the fundamental processes governing the interaction between the biota and its chemical environment, enabling the informed management of human impacts on coastal ecosystems.

Description: New, innovative technologies were developed and integrated within the EU-project COBO (Coastal Ocean Benthic Observatory) to investigate benthic responses to natural and anthropogenic impacts. The Alfred Wegener Institute for Polar and Marine Research (AWI) leads a work-package developing the so-called Integrated Sediment Disturber (ISD) to study the complex interactions between the biota and environmental perturbations and relaxations. The ISD carries three rotating fork-like disturber units able to rework the upper sediment layers at chosen time intervals. An Autonomous Positioning Drive allows the positioning of oxygen micro-sensors within and between the disturbed zones. A camera system continuously monitors all ISD actions. The ISD was deployed for a 2 months experiment in summer/autumn 2006. Sediment sampling has been carried out at the start, after one month and at the end of the long-term deployment. Scientific aims of the experiment are: to investigate benthic community function, with a focus on carbon and nutrient regeneration to investigate response to physical and chemical perturbation (organic additions, resuspension, anoxia) by benthic communities to examine functional resistance and resilience to single and combined pressures

Description: Marine coastal ecosystems are among the most productive and diverse communities on Earth and are of global importance to climate, nutrient budgets, and primary productivity. Yet, these ecosystems, and in particular sedentary benthic (bottom-living) invertebrate communities at their base, are compromised by human-induced stresses, including overfishing, habitat destruction, and pollution. Emerging environmental legislation such as the Water Framework Directive (WFD) has the potential to significantly improve the ecological status of Europes aquatic ecosystems, from rivers to the sea. However, depending upon how it is interpreted and implemented, it has the potential to impact many activities in coastal systems, including flood defence, coastal development, dredging, aquaculture and fishing. There is a critical need for a set of biogeochemical measures to assist in the characterisation of ecological function, status and potential in coastal benthic ecosystems. The FP6-funded Coastal Ocean Benthic Observatories (COBO, http://www.cobo.org.uk) program integrates in situ technologies to monitor benthic habitats, in order to understand how anthropogenic impacts affect benthic ecosystem functioning. As a complement to blind, synoptic sampling and laboratory studies, in situ studies provide rigorous scientific insight into the interactions between the biota (function and diversity) and their chemical and physical environment and the processes regulating this habitat within the context of dynamic processes that occur over many spatial and temporal scales. COBO allows for interdisciplinary, in situ observation and experimentation in these complex, remote and poorly understood ecosystems, both providing fundamental understanding of the interactions between the biota and their environment and facilitating informed management of human impacts on coastal ecosystems. Conceptual frameworks and communication tools are being developed using visualisation software, advanced numerical tools and a DPSIR approach to link scientific results with policy, measures and approaches for coastal ecosystem management.

Description: Coastal ecosystems are particularly vulnerable to anthropogenic perturbation, affecting biodiversity and ecosystem stability and resilience. Shallow water sediments and their associated biota represent a reservoir for biodiversity, hosting resting and reproductive stages of planktonic organisms, and regulating carbon and nutrient biogeochemical cycles. However, the relationship between tightly coupled biological and geochemical processes in this environment is poorly defined with respect to their temporal and spatial variability.The overall objective of COBO is to integrate emerging and innovative technologies from different disciplines (physics, chemistry, biology, imagery) to provide in situ monitoring of sediment habitats, a key component of coastal marine ecosystems, in order to understand complex interactions between the biota (function and diversity) and their chemical environment. Existing technologies have limited spatial and temporal sampling resolutions which has hampered progress in determining key parameters and, in explaining biogeochemical patterns / processes and in modelling ecosystem dynamics. Improved in situ technologies are required to provide rigorous scientific information on processes regulating this unique and fragile habitat and for assessing, controlling and minimising human impact on European coastal waters. The combination of innovative instruments from different scientific disciplines will provide powerful tools to significantly advance our understanding of organism -sediment relations under dynamic coastal conditions and enhance predictive capability.The main activity of COBO is:- Integration of sediment profile imagery (SPI) and Optodes for their simultaneous deployment. This will then allow for the measurement of bi-dimensional fields of oxygen with a visual link to macrofaunal movement.- Development of a scale integrated sediment disturber which working area will be monitored continuously using digital cameras and micro-profilers with oxygen microelectrodes and, at the start and end points, by examining sediment cores.- Development of a chamber capable of regulating oxygen (oxystat) equipped with nitrate sensors.- Integration of manipulated benthic chambers capable of particle and liquid addition and sediment resuspension.- Development of smart and adaptable systems integrating control electronics capable of reaction to external events.- Development of numerical tools consisting of building 2D models of early diagenesis and sediment-organism relationship.