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The Journal of Neuroscience, December 10, 2003, 23(36):11342-11351

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Development/Plasticity/Repair
Mediolateral Compartmentalization of the Cerebellum Is Determined on the "Birth Date" of Purkinje Cells

Mitsuhiro Hashimoto¹ and Katsuhiko Mikoshiba^1,2

¹Laboratory for Developmental Neurobiology, RIKEN BSI, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan, and ²Department of Molecular Neurobiology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan

The adult cerebellum is functionally compartmentalized into clusters along the mediolateral axis (M-L clusters), and a variety of molecular makers are expressed in specific subsets of M-L clusters. These M-L clusters appear to be the basic structure in which cerebellar functions are performed, but the mechanisms by which cerebellar mediolateral compartmentalization is established are still unclear. To address these questions, we examined the development of M-L clusters using replication-defective adenoviral vectors. The adenoviral vectors effectively introduced foreign genes into the neuronal progenitor cells of the cerebellum in a birth date-specific manner, allowing us to observe the native behavior of each cohort of birth date-related progenitor cells. When the adenoviral vectors were injected into the midbrain ventricle of mouse embryos on embryonic days 10.5 (E10.5), E11.5, and E12.5, the virally infected cerebellar progenitor cells developed into Purkinje cells. Notably, the Purkinje cells that shared the same birth date formed specific subsets of M-L clusters in the cerebellum. Each subset of M-L clusters displayed nested and, in part, mutually complementary patterns, and these patterns were unchanged from the late embryonic stage to adulthood, suggesting that Purkinje cell progenitors are fated to form specific subsets of M-L clusters after their birth between E10.5 and E12.5. This study represents the first such direct observation of Purkinje cell development. Moreover, we also show that there is a correlation between the M-L clusters established by the birth date-related Purkinje cells and the domains of engrailed-2, Wnt-7B, L7/pcp2, and EphA4 receptor tyrosine kinase expression.

Key words: compartmentalization; cerebellum; neuronal birth date; Purkinje cell; adenoviral vector; development

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Received May 21, 2003; revised October 21, 2003; accepted October 22, 2003.

This article has been cited by other articles:

				R. Tomioka and K. S. Rockland Improved Golgi-like Visualization in Retrogradely Projecting Neurons after EGFP-Adenovirus Infection in Adult Rat and Monkey J. Histochem. Cytochem., May 1, 2006; 54(5): 539 - 548. [Abstract] [Full Text] [PDF]

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