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The Journal of Neuroscience, May 27, 2009, 29(21):7079-7091; doi:10.1523/JNEUROSCI.0957-09.2009
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Development/Plasticity/Repair
Laminar Fate and Phenotype Specification of Cerebellar GABAergic Interneurons
Ketty Leto,1 * Alice Bartolini,1 * Yukio Yanagawa,2 Kunihiko Obata,3 Lorenzo Magrassi,4 Karl Schilling,5 andFerdinando Rossi1 1Department of Neuroscience and Rita Levi-Montalcini Center for Brain Repair, Neuroscience Institute of Turin, University of Turin, I-10125 Turin, Italy, 2Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan, 3RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan, 4Neurosurgery, Department of Surgical Sciences, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, University of Pavia, 27100 Pavia, Italy, and 5Anatomisches Institut, Anatomie und Zellbiologie, Rheinische Friedrich-Wilhelms-Universität, 53115 Bonn, Germany
Correspondence should be addressed to Ferdinando Rossi, Rita Levi-Montalcini Center for Brain Repair, Department of Neuroscience, Section of Physiology, University of Turin, Corso Raffaello 30, I-10125 Turin, Italy. Email: ferdinando.rossi{at}unito.it
In most CNS regions, the variety of inhibitory interneurons originates from separate pools of progenitors residing in discrete germinal domains, where they become committed to specific phenotypes and positions during their last mitosis. We show here that GABAergic interneurons of the rodent cerebellum are generated through a different mechanism. Progenitors for these interneurons delaminate from the ventricular neuroepithelium of the embryonic cerebellar primordium and continue to proliferate in the prospective white matter during late embryonic and postnatal development. Young postmitotic interneurons do not migrate immediately to their final destination, but remain in the prospective white matter for several days. The different interneuron categories are produced according to a continuous inside-out positional sequence, and cell identity and laminar placement in the cerebellar cortex are temporally related to birth date. However, terminal commitment does not occur while precursors are still proliferating, and postmitotic cells heterochronically transplanted to developing cerebella consistently adopt host-specific phenotypes and positions. However, solid grafts of prospective white matter implanted into the adult cerebellum, when interneuron genesis has ceased, produce interneuron types characteristic of the donor age. Therefore, specification of cerebellar GABAergic interneurons occurs through a hitherto unknown process, in which postmitotic neurons maintain broad developmental potentialities and their phenotypic choices are dictated by instructive cues provided by the microenvironment of the prospective white matter. Whereas in most CNS regions the repertoire of inhibitory interneurons is produced by recruiting precursors from different origins, in the cerebellum it is achieved by creating phenotypic diversity from a single source.
Received Feb. 25, 2009; revised April 29, 2009; accepted May 2, 2009.
Correspondence should be addressed to Ferdinando Rossi, Rita Levi-Montalcini Center for Brain Repair, Department of Neuroscience, Section of Physiology, University of Turin, Corso Raffaello 30, I-10125 Turin, Italy. Email: ferdinando.rossi{at}unito.it
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