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      Fibroblast growth factor signalling controls nervous system patterning and pigment cell formation in Ciona intestinalis

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          Abstract

          During the development of the central nervous system (CNS), combinations of transcription factors and signalling molecules orchestrate patterning, specification and differentiation of neural cell types. In vertebrates, three types of melanin-containing pigment cells, exert a variety of functional roles including visual perception. Here we analysed the mechanisms underlying pigment cell specification within the CNS of a simple chordate, the ascidian Ciona intestinalis. Ciona tadpole larvae exhibit a basic chordate body plan characterized by a small number of neural cells. We employed lineage-specific transcription profiling to characterize the expression of genes downstream of fibroblast growth factor signalling, which govern pigment cell formation. We demonstrate that FGF signalling sequentially imposes a pigment cell identity at the expense of anterior neural fates. We identify FGF-dependent and pigment cell-specific factors, including the small GTPase, Rab32/38 and demonstrated its requirement for the pigmentation of larval sensory organs.

          Abstract

          The fibroblast growth factor (FGF) signalling pathway specifies the fate of pigmented cells in the ascidian Ciona intestinalis. Here, the authors obtain lineage-specific transcription profiles of pigment precursor cells and identify FGF downstream genes involved in central nervous system patterning, and the specification and differentiation of pigmented cells.

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          The Bioperl toolkit: Perl modules for the life sciences.

          The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.
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            The transcriptional network for mesenchymal transformation of brain tumors

            Inference of transcriptional networks that regulate transitions into physiologic or pathologic cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumor aggressiveness in human malignant glioma but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here, we show that reverse-engineering and unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPβ and Stat3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPβ and Stat3 reprograms neural stem cells along the aberrant mesenchymal lineage whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumor aggressiveness. In human glioma, expression of C/EBPβ and Stat3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results reveal that activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells.
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              Tunicates and not cephalochordates are the closest living relatives of vertebrates.

              Tunicates or urochordates (appendicularians, salps and sea squirts), cephalochordates (lancelets) and vertebrates (including lamprey and hagfish) constitute the three extant groups of chordate animals. Traditionally, cephalochordates are considered as the closest living relatives of vertebrates, with tunicates representing the earliest chordate lineage. This view is mainly justified by overall morphological similarities and an apparently increased complexity in cephalochordates and vertebrates relative to tunicates. Despite their critical importance for understanding the origins of vertebrates, phylogenetic studies of chordate relationships have provided equivocal results. Taking advantage of the genome sequencing of the appendicularian Oikopleura dioica, we assembled a phylogenomic data set of 146 nuclear genes (33,800 unambiguously aligned amino acids) from 14 deuterostomes and 24 other slowly evolving species as an outgroup. Here we show that phylogenetic analyses of this data set provide compelling evidence that tunicates, and not cephalochordates, represent the closest living relatives of vertebrates. Chordate monophyly remains uncertain because cephalochordates, albeit with a non-significant statistical support, surprisingly grouped with echinoderms, a hypothesis that needs to be tested with additional data. This new phylogenetic scheme prompts a reappraisal of both morphological and palaeontological data and has important implications for the interpretation of developmental and genomic studies in which tunicates and cephalochordates are used as model animals.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                05 September 2014
                : 5
                : 4830
                Affiliations
                [1 ]Cellular and Developmental Biology Laboratory, Stazione Zoologica Anton Dorhn, Villa Comunale , 80121 Napoli, Italy
                [2 ]Center for Developmental Genetics, Department of Biology, New York University , New York, New York 1003, USA
                [3 ]Telethon Institute of Genetics and Medicine (TIGEM) , Via P. Castellino 111, 80131 Naples, Italy
                [4 ]Animal Physiology and Evolution Laboratory, Stazione Zoologica Anton Dorhn, Villa Comunale , 80121 Napoli, Italy
                Author notes
                Article
                ncomms5830
                10.1038/ncomms5830
                4164782
                25189217
                8436a8aa-5723-4281-852c-ba995588d7c5
                Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 02 December 2013
                : 25 July 2014
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