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      Ets-1 Confers Cranial Features on Neural Crest Delamination

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      1 , 2 , 1 , 2 , 1 , 2 , *
      PLoS ONE
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          Abstract

          Neural crest cells (NCC) have the particularity to invade the environment where they differentiate after separation from the neuroepithelium. This process, called delamination, is strikingly different between cranial and trunk NCCs. If signalings controlling slow trunk delamination start being deciphered, mechanisms leading to massive and rapid cranial outflow are poorly documented. Here, we show that the chick cranial NCCs delamination is the result of two events: a substantial cell mobilization and an epithelium to mesenchyme transition (EMT). We demonstrate that ets-1, a transcription factor specifically expressed in cranial NCCs, is responsible for the former event by recruiting massively cranial premigratory NCCs independently of the S-phase of the cell cycle and by leading the gathered cells to straddle the basal lamina. However, it does not promote the EMT process alone but can cooperate with snail-2 (previously called slug) to this event. Altogether, these data lead us to propose that ets-1 plays a pivotal role in conferring specific cephalic characteristics on NCC delamination.

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          Most cited references55

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          Epithelial-mesenchymal transitions in development and pathologies.

          The epithelial-mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms. This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma. The molecular mechanisms of EMT were primarily studied in epithelial cell lines, leading to the discovery of transduction pathways involved in the loss of epithelial cell polarity and the acquisition of a variety of mesenchymal phenotypic traits. Similar mechanisms have also been uncovered in vivo in different species, showing that EMT is controlled by remarkably well-conserved mechanisms. Current studies further emphasise the critical importance of EMT and provide a better molecular and functional definition of mesenchymal cells and how they emerged >500 million years ago as a key event in evolution.
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            Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.

            The p16INK4a cyclin-dependent kinase inhibitor is implicated in replicative senescence, the state of permanent growth arrest provoked by cumulative cell divisions or as a response to constitutive Ras-Raf-MEK signalling in somatic cells. Some contribution to senescence presumably underlies the importance of p16INK4a as a tumour suppressor but the mechanisms regulating its expression in these different contexts remain unknown. Here we demonstrate a role for the Ets1 and Ets2 transcription factors based on their ability to activate the p16INK4a promoter through an ETS-binding site and their patterns of expression during the lifespan of human diploid fibroblasts. The induction of p16INK4a by Ets2, which is abundant in young human diploid fibroblasts, is potentiated by signalling through the Ras-Raf-MEK kinase cascade and inhibited by a direct interaction with the helix-loop-helix protein Id1 (ref. 11). In senescent cells, where the Ets2 levels and MEK signalling decline, the marked increase in p16INK4a expression is consistent with the reciprocal reduction of Id1 and accumulation of Ets1.
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              Molecular biology of the Ets family of transcription factors.

              The Ets family of transcription factors characterized by an evolutionarily-conserved DNA-binding domain regulates expression of a variety of viral and cellular genes by binding to a purine-rich GGAA/T core sequence in cooperation with other transcriptional factors and co-factors. Most Ets family proteins are nuclear targets for activation of Ras-MAP kinase signaling pathway and some of them affect proliferation of cells by regulating the immediate early response genes and other growth-related genes. Some of them also regulate apoptosis-related genes. Several Ets family proteins are preferentially expressed in specific cell lineages and are involved in their development and differentiation by increasing the enhancer or promoter activities of the genes encoding growth factor receptors and integrin families specific for the cell lineages. Many Ets family proteins also modulate gene expression through protein-protein interactions with other cellular partners. Deregulated expression or formation of chimeric fusion proteins of Ets family due to proviral insertion or chromosome translocation is associated with leukemias and specific types of solid tumors. Several Ets family proteins also participate in malignancy of tumor cells including invasion and metastasis by activating the transcription of several protease genes and angiogenesis-related genes.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS ONE
                plos
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2007
                7 November 2007
                : 2
                : 11
                : e1142
                Affiliations
                [1 ]Université Pierre et Marie Curie - Paris6, UMR 7622, Laboratoire de Biologie du Développement, Paris, France
                [2 ]CNRS, UMR 7622 Laboratoire de Biologie du Développement, Paris, France
                Baylor College of Medicine, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: Muriel.Altabef@ 123456snv.jussieu.fr

                Conceived and designed the experiments: MA ET JD. Performed the experiments: MA ET. Analyzed the data: MA ET. Contributed reagents/materials/analysis tools: MA ET. Wrote the paper: MA ET.

                [¤]

                Current address: Department of Anatomy and Developmental Biology, University College London, London, United Kingdom

                Article
                07-PONE-RA-01041R1
                10.1371/journal.pone.0001142
                2043494
                17987123
                77376c5c-5206-49bf-9dc7-c2155357e4f5
                Théveneau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 6 April 2007
                : 17 October 2007
                Page count
                Pages: 16
                Categories
                Research Article
                Developmental Biology/Embryology
                Developmental Biology/Morphogenesis and Cell Biology
                Developmental Biology/Neurodevelopment

                Uncategorized
                Uncategorized

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