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      Microtubule dynamics in neuronal morphogenesis

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          Abstract

          Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development.

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          Dynamic instability of microtubule growth.

          We report here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently. This dynamic instability is a general property of microtubules and may be fundamental in explaining cellular microtubule organization.
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            Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons.

            Recently, we and others reported that the doublecortin gene is responsible for X-linked lissencephaly and subcortical laminar heterotopia. Here, we show that Doublecortin is expressed in the brain throughout the period of corticogenesis in migrating and differentiating neurons. Immunohistochemical studies show its localization in the soma and leading processes of tangentially migrating neurons, and a strong axonal labeling is observed in differentiating neurons. In cultured neurons, Doublecortin expression is highest in the distal parts of developing processes. We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. Our data suggest that the cortical dysgeneses associated with the loss of Doublecortin function might result from abnormal cytoskeletal dynamics in neuronal cell development.
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              Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons.

              Doublecortin (DCX) is required for normal migration of neurons into the cerebral cortex, since mutations in the human gene cause a disruption of cortical neuronal migration. To date, little is known about the distribution of DCX protein or its function. Here, we demonstrate that DCX is expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development. DCX protein localization overlaps with microtubules in cultured primary cortical neurons, and this overlapping expression is disrupted by microtubule depolymerization. DCX coassembles with brain microtubules, and recombinant DCX stimulates the polymerization of purified tubulin. Finally, overexpression of DCX in heterologous cells leads to a dramatic microtubule phenotype that is resistant to depolymerization. Therefore, DCX likely directs neuronal migration by regulating the organization and stability of microtubules.
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                Author and article information

                Journal
                Open Biol
                Open Biol
                RSOB
                royopenbio
                Open Biology
                The Royal Society
                2046-2441
                July 2013
                July 2013
                : 3
                : 7
                : 130061
                Affiliations
                [1 ]Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine , Nagoya 466-8550, Japan
                [2 ]Department of Molecular Genetics, Weizmann Institute of Science , 76100 Rehovot, Israel
                [3 ]Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo , Tokyo 113-0033, Japan
                Author notes
                Article
                rsob130061
                10.1098/rsob.130061
                3728923
                23864552
                39a9833e-89f7-4572-84e0-34bde10ce732

                © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : 7 April 2013
                : 7 June 2013
                Categories
                1001
                33
                58
                133
                Review
                Review Article
                Custom metadata
                July 2013

                Life sciences
                microtubules,polarity,centrosome,axon,migration,neuron
                Life sciences
                microtubules, polarity, centrosome, axon, migration, neuron

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