Role of BMP, FGF, Calcium Signaling, and Zic Proteins in Vertebrate Neuroectodermal Differentiation

More than a decade has passed since Zic family zinc finger proteins were discovered to be transcription factors controlling neuroectodermal differentiation (neural induction) in Xenopus laevis embryos. Although BMP-signal blocking has been shown to be a major upregulator of Zic genes in neuroectodermal differentiation, recent studies have revealed that FGF signaling and intracellular calcium elevation are also involved in regulating the expression of Zic genes. Different regulatory mechanisms have been found for the Zic1 and Zic3 genes, raising the possibility that functional synergism between them partly accounts for the integration of BMP-signal blocking and FGF signaling in neuroectodermal differentiation. Furthermore, mammalian Zic1 and Zic3 have been found to be neural-cell-fate-inducing and pluripotency-maintaining factors, respectively, leading us to the intriguing question of whether the mechanism underlying amphibian neuroectodermal differentiation is applicable to mammals. Comprehensive understanding of the Zic family genes is therefore essential for the study of the neuroectodermal differentiation and stem cell biology

A mRNA landscape of bovine embryos after standard and MAPK-inhibited culture conditions: a comparative analysis.

BACKGROUND: Genes and signalling pathways involved in pluripotency have been studied extensively in mouse and human pre-implantation embryos and embryonic stem (ES) cells. The unsuccessful attempts to generate ES cell lines from other species including cattle suggests that other genes and pathways are involved in maintaining pluripotency in these species. To investigate which genes are involved in bovine pluripotency, expression profiles were generated from morula, blastocyst, trophectoderm and inner cell mass (ICM) samples using microarray analysis. As MAPK inhibition can increase the NANOG/GATA6 ratio in the inner cell mass, additionally blastocysts were cultured in the presence of a MAPK inhibitor and changes in gene expression in the inner cell mass were analysed. RESULTS: Between morula and blastocyst 3,774 genes were differentially expressed and the largest differences were found in blastocyst up-regulated genes. Gene ontology (GO) analysis shows lipid metabolic process as the term most enriched with genes expressed at higher levels in blastocysts. Genes with higher expression levels in morulae were enriched in the RNA processing GO term. Of the 497 differentially expressed genes comparing ICM and TE, the expression of NANOG, SOX2 and POU5F1 was increased in the ICM confirming their evolutionary preserved role in pluripotency. Several genes implicated to be involved in differentiation or fate determination were also expressed at higher levels in the ICM. Genes expressed at higher levels in the ICM were enriched in the RNA splicing and regulation of gene expression GO term. Although NANOG expression was elevated upon MAPK inhibition, SOX2 and POU5F1 expression showed little increase. Expression of other genes in the MAPK pathway including DUSP4 and SPRY4, or influenced by MAPK inhibition such as IFNT, was down-regulated. CONCLUSION: The data obtained from the microarray studies provide further insight in gene expression during bovine embryonic development. They show an expression profile in pluripotent cells that indicates a pluripotent, epiblast-like state. The inability to culture ICM cells as stem cells in the presence of an inhibitor of MAPK activity together with the reported data indicates that MAPK inhibition alone is not sufficient to maintain a pluripotent character in bovine cells

Invariance principles for non-uniform random mappings and trees

In the context of uniform random mappings of an n-element set to itself, Aldous and Pitman (1994) established a functional invariance principle, showing that many n!1 limit distributions can be described as distributions of suitable functions of reflecting Brownian bridge. To study non-uniform cases, in this paper we formulate a sampling invariance principle in terms of iterates of a fixed number of random elements. We show that the sampling invariance principle implies many, but not all, of the distributional limits implied by the functional invariance principle. We give direct verifications of the sampling invariance principle in two successive generalizations of the uniform case, to p-mappings (where elements are mapped to i.i.d. non-uniform elements) and P-mappings (where elements are mapped according to a Markov matrix). We compare with parallel results in the simpler setting of random trees

Uncertainty Challenge in Geospatial Analysis: An Approximation from the Land Use Cover Change Modelling Perspective

All data and geospatial analyses come with uncertainty. Although its importance has been widely recognized, uncertainty issues are still not correctly addressed in most of the current geospatial research. This chapter aims to provide an overview of the concepts, sources and tools to manage the uncertainty in geospatial analysis. To this end, we intend to increase the awareness about the importance of uncertainty for all geospatial data and analyses. Due to time and chapter length considerations, we address this topic from the Land Use Cover Change Modelling perspective.Agencia Estatal de InvestigaciónDepto. de GeografíaFac. de Geografía e HistoriaTRUEpu