Granule Cell Migration and Differentiation
In the developing cerebellum, granule cells migrate from their birth place to their final destination. The active translocation of granule cells is essential for the formation of cerebellar cortical layers and their proper differentiation. This chapter wi
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Abstract
In the developing cerebellum, granule cells migrate from their birth place to their final destination. The active translocation of granule cells is essential for the formation of cerebellar cortical layers and their proper differentiation. This chapter will review (1) how granule cells migrate from their origin to their resident destinations in the developing cerebellum, (2) the mechanisms involved in normal and abnormal migration of granule cells, and (3) the mechanisms underlying the differentiation of granule cells.
Introduction After final cell division, postmitotic neurons migrate from their sites of origin to their final destinations, where they reside during their entire adult life. This movement of immature neurons is a fundamental cellular event essential for building large neuronal assemblies (Valiente and Marin 2010). Distinct genetic mutations and environmental toxins can affect neuronal migration in humans and result in abnormal development of the brain, leading to neurological disorders (Guerrini and Parrini 2010). During the last five decades, granule cell migration has been extensively studied and used as a model system for neuronal migration. This is because the mechanisms underlying granule cell migration are utilized during the migration of immature neurons in other brain regions (Komuro and Rakic 1998b; Jiang et al. 2008). The role of neuron–glia interaction in neuronal migration was first discovered in the migration of granule cells along the Bergmann glial processes in the
Y. Komuro • J.K. Fahrion • K.D. Foote • K.B. Fenner • T. Kumada • N. Ohno • H. Komuro (*) Department of Neurosciences, NC30, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA e-mail: [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] M. Manto, D.L. Gruol, J.D. Schmahmann, N. Koibuchi, F. Rossi (eds.), 107 Handbook of the Cerebellum and Cerebellar Disorders, DOI 10.1007/978-94-007-1333-8_7, # Springer Science+Business Media Dordrecht 2013
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developing cerebellum (Rakic 1971). This discovery led to the findings that in the developing cerebrum, immature neurons use radial glial processes as a scaffold for their migration. Likewise, the role of cell adhesion molecules in neuronal cell migration was first discovered in granule cells (Rakic et al. 1994). To date, wide varieties of cell adhesion molecules, which play a critical role in neuronal cell migration, have been identified in other regions of the brain. Moreover, the regulation of neuronal cell migration by neurotransmitters was first reported in granule cell migration (Komuro and Rakic 1993), followed by the discovery showing the key role of neurotransmitters in the migration of cerebral neurons. This chapter will first describe the recent findings revealing that granule cells exhibit cortical layer-specific changes in their migration. It will then discuss how the cortical layer-specific migration of granule cells is
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