Correlating Global Gene Regulation to Angiogenesis in the Developing Chick Extra-Embryonic Vascular System

International audienceBACKGROUND: Formation of blood vessels requires the concerted regulation of an unknown number of genes in a spatial-, time- and dosage-dependent manner. Determining genes, which drive vascular maturation is crucial for the identification of new therapeutic targets against pathological angiogenesis. METHOLOGY/PRINCIPAL FINDINGS: We accessed global gene regulation throughout maturation of the chick chorio-allantoic membrane (CAM), a highly vascularized tissue, using pan genomic microarrays. Seven percent of analyzed genes showed a significant change in expression (>2-fold, FDR<5%) with a peak occurring from E7 to E10, when key morphogenetic and angiogenic genes such as BMP4, SMO, HOXA3, EPAS1 and FGFR2 were upregulated, reflecting the state of an activated endothelium. At later stages, a general decrease in gene expression occurs, including genes encoding mitotic factors or angiogenic mediators such as CYR61, EPAS1, MDK and MYC. We identified putative human orthologs for 77% of significantly regulated genes and determined endothelial cell enrichment for 20% of the orthologs in silico. Vascular expression of several genes including ENC1, FSTL1, JAM2, LDB2, LIMS1, PARVB, PDE3A, PRCP, PTRF and ST6GAL1 was demonstrated by in situ hybridization. Up to 9% of the CAM genes were also overexpressed in human organs with related functions, such as placenta and lung or the thyroid. 21-66% of CAM genes enriched in endothelial cells were deregulated in several human cancer types (P<.0001). Interfering with PARVB (encoding parvin, beta) function profoundly changed human endothelial cell shape, motility and tubulogenesis, suggesting an important role of this gene in the angiogenic process. CONCLUSIONS/SIGNIFICANCE: Our study underlines the complexity of gene regulation in a highly vascularized organ during development. We identified a restricted number of novel genes enriched in the endothelium of different species and tissues, which may play crucial roles in normal and pathological angiogenesis

Holocene demographic fluctuations, climate and erosion in the Mediterranean: A meta data-analysis

As part of the Changing the Face of the Mediterranean Project, we consider how human pressure and concomitant erosion has affected a range of Mediterranean landscapes between the Neolithic and, in some cases, the post-medieval period. Part of this assessment comprises an investigation of relationships among palaeodemographic data, evidence for vegetation change and some consideration of rapid climate change events. The erosion data include recent or hitherto unpublished work from the authors. Where possible, we consider summed probabilities of 14C dates as well as the first published synthesis of all known optically stimulated luminescence dated sequences. The results suggest that while there were some periods when erosion took place contemporaneously across a number of regions, possibly induced by climate changes, more often than not, we see a complex and heterogeneous interplay of demographic and environmental changes that result in a mixed pattern of erosional activity across the Mediterranean

Archaeological evidence for the first Mesolithic occupation of the Western Isles of Scotland

The examination of eroding coastal dunes at the prehistoric site of Northton, Harris, has produced the first archaeological evidence of Mesolithic activity in the Western Isles in the form of two midden-related deposits. The first phase of Mesolithic activity is dated to 7060/6650 cal. BC based on AMS dating of charred hazelnut shells. This discovery appears to validate the frequent pollen-based inferences of Mesolithic impact for the area and, as predicted, allows the Atlantic fringe of Scotland to become part of the European Mesolithic mainstream. A detailed pedological analysis also suggests that these early midden layers may have been amended during the Neolithic period as part of a possible phase of cultivation