Studies of mouse cerebellar compartmentation
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2008
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Abstract
The cerebellum is an appealing model system for studying pattern formation. Despite its uniform histology, there is a complex underlying pattern of parasagittal stripes involving multiple cell types. This patterning is thought to be a highly conserved feature both during development and in the adult. To explore this issue, I first present that the expression of gamma-aminobutyric acid B receptor 2 is in an array of Purkinje cell stripes identical to that revealed by anti-zebrin II, which is the most studied cerebellar compartmentation antigen. Secondly, I present expression data showing that the pattern of phospholipase CB4 expression, a zebrin II-imrnunonegative Purkinje cell marker, can be traced continuously from the embryo to the adult. Thirdly, I describe a gene, Early Bcell factor 2 (EBF2) that suppresses the zebrin II-imrnunopositive phenotype. EBF2 expression is confined to the zebrin II-imrnunonegative population and zebrin II is uniformly expressed in the Ebj2 null cerebellum due to a combination of selective Purkinje cell death and ectopic expression of genes normally restricted to the zebrin IIimrnunonegative Purkinje cell subset. Fourthly, I investigated the topographical relationship between zebrin II compartmentation and the distribution of unipolar brush cells. The data suggest that unipolar brush cell somata become regionally restricted through interactions with specific Purkinje cell subtypes. Finally, the cerebellar nuclei (CN) are the next relay stage in the cerebellar circuit and receive the sole output from Purkinje cells. However, there is no molecular complexity in the CN equivalent to that in the cerebellar cortex. To begin to address this gap, I first built an adult CN map by using a novel marker - kinesin light chain 3. Then, I combined the use of various antigens and transgenes to reveal a complex heterogeneity in the mouse CN that can be used to subdivide the CN into twelve reproducible expression domains. Similar heterogeneity can also be revealed during development: the medial nuclei are constructed from two separate neuronal subsets, each with a distinct embryological origin. These data suggest that a complex topography similar to that seen in the cerebellar cortex, is also present in the CN.
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Bibliography: p. 321-386
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Chung, S. (2008). Studies of mouse cerebellar compartmentation (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/2265