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      The centrosome neither persistently leads migration nor determines the site of axonogenesis in migrating neurons in vivo

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          Abstract

          In vivo analysis of subcellular dynamics in the zebrafish cerebellum provides new insights into centrosome positioning during vertebrate brain differentiation.

          Abstract

          The position of the centrosome ahead of the nucleus has been considered crucial for coordinating neuronal migration in most developmental situations. The proximity of the centrosome has also been correlated with the site of axonogenesis in certain differentiating neurons. Despite these positive correlations, accumulating experimental findings appear to negate a universal role of the centrosome in determining where an axon forms, or in leading the migration of neurons. To further examine this controversy in an in vivo setting, we have generated cell type–specific multi-cistronic gene expression to monitor subcellular dynamics in the developing zebrafish cerebellum. We show that migration of rhombic lip–derived neurons is characterized by a centrosome that does not persistently lead the nucleus, but which is instead regularly overtaken by the nucleus. In addition, axonogenesis is initiated during the onset of neuronal migration and occurs independently of centrosome proximity. These in vivo data reveal a new temporal orchestration of organelle dynamics and provide important insights into the variation in intracellular processes during vertebrate brain differentiation.

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          Most cited references48

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          Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.

          Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.
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            Flies without centrioles.

            Centrioles and centrosomes have an important role in animal cell organization, but it is uncertain to what extent they are essential for animal development. The Drosophila protein DSas-4 is related to the human microcephaly protein CenpJ and the C. elegans centriolar protein Sas-4. We show that DSas-4 is essential for centriole replication in flies. DSas-4 mutants start to lose centrioles during embryonic development, and, by third-instar larval stages, no centrioles or centrosomes are detectable. Mitotic spindle assembly is slow in mutant cells, and approximately 30% of the asymmetric divisions of larval neuroblasts are abnormal. Nevertheless, mutant flies develop with near normal timing into morphologically normal adults. These flies, however, have no cilia or flagella and die shortly after birth because their sensory neurons lack cilia. Thus, centrioles are essential for the formation of centrosomes, cilia, and flagella, but, remarkably, they are not essential for most aspects of Drosophila development.
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              Neuronal polarity: from extracellular signals to intracellular mechanisms.

              After they are born and differentiate, neurons break their previous symmetry, dramatically change their shape, and establish two structurally and functionally distinct compartments - axons and dendrites - within one cell. How do neurons develop their morphologically and molecularly distinct compartments? Recent studies have implicated several signalling pathways evoked by extracellular signals as having essential roles in a number of aspects of neuronal polarization.
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                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                15 November 2010
                : 191
                : 4
                : 875-890
                Affiliations
                Helmholtz Zentrum München German Research Center for Environmental Health, Institute of Developmental Genetics, 85764 Munich-Neuherberg, Germany
                Author notes
                Correspondence to Reinhard W. Köster: Reinhard.Koester@ 123456helmholtz-muenchen.de

                M. Distel’s present address is Natural Sciences Building, Room 6310, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093.

                K. Volkmann’s present address is The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, England, UK.

                Article
                201004154
                10.1083/jcb.201004154
                2983064
                21059852
                aa5035d6-3823-4a66-bd33-9136b28d2af5
                © 2010 Distel et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                : 29 April 2010
                : 14 October 2010
                Categories
                Research Articles
                Article

                Cell biology
                Cell biology

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