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Analysis of Gene Expression in the Normal and Malignant Cerebellum

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710

The developing nervous system consists of a small number of multipotent precursors that undergo extensive proliferation to generate the neurons and glia that make up the adult brain. Elucidating the mechanisms that control the growth and differentiation of these cells is important not only for understanding normal neural development but also for understanding the etiology of central nervous system tumors. A particularly striking example of this is in the cerebellum. Recent studies have suggested that the Sonic hedgehog-Patched signaling pathway plays a critical role in regulating the proliferation of cerebellar granule cell precursors and is also a major target of mutation in the cerebellar tumor medulloblastoma. In light of these observations, identification of additional genes that control cerebellar growth and differentiation is likely to provide important insight into the basis of cerebellar tumors. Similarly, analysis of gene expression in medulloblastoma will no doubt shed light on previously unknown signaling pathways that regulate normal cerebellar development. The advent of high-throughput gene expression analysis techniques — such as adapter-tagged competitive polymerase chain reaction (ATAC-PCR), serial analysis of gene expression (SAGE), and DNA microarrays — makes identification of such genes faster and easier than ever before. This review summarizes recent studies of gene expression in the cerebellum and discusses the value of such approaches for understanding development and tumorigenesis in this tissue.

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