Zones and Stripes: Development of Cerebellar Topography

Abstract

Cerebellar architecture is organized around the Purkinje cell. Purkinje cells in the mouse cerebellum come in many different subtypes, organized first into four transverse zones and then further grouped into hundreds of reproducible topographical units – stripes. Stripes are identified by their functional properties, connectivity, and expression profiles. The molecular pattern of stripes is highly reproducible between individuals and conserved through evolution. Pattern formation in the cerebellar cortex is a multistage process that begins with the generation of the Purkinje cells in the ventricular zone (VZ) of the fourth ventricle. During this stage or shortly after, Purkinje cell subtypes are specified toward specific positions. Purkinje cells migrate from the VZ to form an array of clusters that form the framework for cerebellar topography. At around birth these clusters disperse, triggered by a Reelin signaling pathway, to form the adult stripe array. The chapter will begin with a brief overview of adult cerebellar topography, primarily focusing on the mouse cerebellum, and then discuss the cellular and molecular mechanisms that establish these remarkable patterns. R.V. Sillitoe Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine 812 Kennedy Center, 1410 Pelham Parkway South, Bronx, NY, 10461, USA e-mail: roy.sillitoe@einstein.yu.edu R. Hawkes (*) Department of Cell Biology and Anatomy Genes and Development Research Group, and Hotchkiss Brain Institute, The University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada e-mail: rhawkes@ucalgary.ca M. Manto, D.L. Gruol, J.D. Schmahmann, N. Koibuchi, F. Rossi (eds.), Handbook of the Cerebellum and Cerebellar Disorders, DOI 10.1007/978-94-007-1333-8_3, # Springer Science+Business Media Dordrecht 2013 43 The Architecture of the Adult Cerebellar Cortex The adult mouse cerebellum is shown in Fig. 3.1, immunoperoxidase stained for the antigen zebrin II (Brochu et al. 1990: zebrin II 1⁄4 aldolase C (AldoC) – Ahn et al. 1994). There are two subsets of Purkinje cells: zebrin II-immunopositive (zebrin II+) and zebrin II-immunonegative (zebrin II-). Purkinje cells in each subset are aligned to form an alternating array of parasagittal stripes (Brochu et al. 1990; Sillitoe and Hawkes 2002). Stripes are reproducible between individuals and symmetrically distributed about the midline (Hawkes et al. 1985; Hawkes and Leclerc 1987; Brochu et al. 1990). Zebrin II+ stripes are numbered as P1+ P7+ from the midline laterally, and the intervening zebrin IIstripes are numbered with reference to the medial zebrin II+ stripe (i.e., P1lies immediately lateral to P1+, etc.). In the vermis, four transverse domains in the anterior–posterior axis are identified by zebrin II expression: the striped anterior zone (AZ: lobules I–V), the uniformly zebrin II+ central zone (CZ: lobules VI–VII), the striped posterior zone (PZ: lobules VIII–dorsal IX), and the uniformly zebrin II+ nodular zone (NZ: lobules IX ventral and X: Ozol et al. 1999). A similar alternation of zones is seen in the hemispheres (Sarna et al. 2006).