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The Journal of Neuroscience, July 16, 2008, 28(29):7387-7398; doi:10.1523/JNEUROSCI.1942-08.2008
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Development/Plasticity/Repair
SCLIP Is Crucial for the Formation and Development of the Purkinje Cell Dendritic Arbor
Fabienne E. Poulain,1,2,4 Stéphanie Chauvin,1,2,4 Rosine Wehrlé,3,4 Mathieu Desclaux,4,5 Jacques Mallet,4,5 Guilan Vodjdani,4,5 Isabelle Dusart,3,4 * andAndré Sobel1,2,4 * 1Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) 839, 2Institut du Fer à Moulin, 3Centre National de la Recherche Scientifique (CNRS), UMR7102–Neurobiologie des Processus Adaptatifs, and 4Université Pierre et Marie Curie, Université Paris 06, F-75005 Paris, France, and 5CNRS, UMR7091–Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, F-75013 Paris, France
Correspondence should be addressed to Dr. André Sobel, Institut National de la Santé et de la Recherche Médicale/Université Pierre et Marie Curie, Unité Mixte de Recherche S 839, Institut du Fer à Moulin, 17 rue du Fer à Moulin, F-75005 Paris, France. Email: sobel{at}fer-a-moulin.inserm.fr
Cerebellar Purkinje cells elaborate one of the most complex dendritic arbors among neurons to integrate the numerous signals they receive from the cerebellum circuitry. Their dendritic differentiation undergoes successive, tightly regulated phases of development involving both regressive and growth events. Although many players regulating the late phases of Purkinje cell dendritogenesis have been identified, intracellular factors controlling earlier phases of dendritic development remain mostly unknown. In this study, we explored the biological properties and functions of SCLIP, a protein of the stathmin family, in Purkinje cell dendritic differentiation and cerebellum development. Unlike the other stathmins, SCLIP is strongly expressed in Purkinje cells during cerebellar development and accumulates in their dendritic processes at a critical period of their formation and outgrowth. To reveal SCLIP functions, we developed a lentiviral-mediated approach on cerebellar organotypic cultures to inhibit or increase its expression in Purkinje cells in their tissue environment. Depletion of SCLIP promoted retraction of the Purkinje cell primitive process and then prevented the formation of new dendrites at early stages of postnatal development. It also prevented their elongation and branching at later phases of differentiation. Conversely, SCLIP overexpression promoted dendritic branching and development. Together, our results demonstrate for the first time that SCLIP is crucial for both the formation and proper development of Purkinje cell dendritic arbors. SCLIP appears thus as a novel and specific factor that controls the early phases of Purkinje cell dendritic differentiation during cerebellum development.
Key words: dendritogenesis; differentiation; stathmin; cerebellar organotypic cultures; lentiviral vector; cerebellum development
Received Dec. 31, 2007; revised June 9, 2008; accepted June 9, 2008.
Correspondence should be addressed to Dr. André Sobel, Institut National de la Santé et de la Recherche Médicale/Université Pierre et Marie Curie, Unité Mixte de Recherche S 839, Institut du Fer à Moulin, 17 rue du Fer à Moulin, F-75005 Paris, France. Email: sobel{at}fer-a-moulin.inserm.fr
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J. Neurosci. 2008 28: i.[Full Text]
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