Analysis of Gene Networks in Cerebellar Development
The purpose of this chapter is to provide a brief overview of the major gene networks that control cerebellum development. To simplify this task, all developmental control genes relevant to the cerebellum have been grouped into four categories based on 13
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Abstract
The purpose of this chapter is to provide a brief overview of the major gene networks that control cerebellum development. To simplify this task, all developmental control genes relevant to the cerebellum have been grouped into four categories based on 13 spontaneous mouse mutations with cerebellar developmental defects and for which the aberrant gene has been identified. These categories include genetic switch genes and genes for morphogenesis, physiology, and metabolism. Three distinct gene targetome studies are discussed in order to introduce some signature networks of major importance to cerebellum development based on the genetic switches En2, Atoh1 (Math1), and Rora (RORa). Similarly, array approaches have begun to reveal gene expression changes due to mutations in physiology and metabolism genes, such as Kcnj6 (Girk2) and Agtpbp1 (Nna1), respectively. These studies are revealing the interplay between transcription, morphogenetic factors, physiology, and metabolism during development. Lastly, genomics and informatics approaches are uncovering new markers of all cerebellar cell types at all stages that will be useful in the future for further clarifying the complex and often reciprocal nature of developmental mechanisms in the nervous system.
Introduction The cerebellum has been a central source of information concerning the identity and function of key gene networks controlling brain development and function. The explosion of knowledge about such networks began with the visionary analysis and
J. Oberdick Department of Neuroscience & Center for Molecular Neurobiology, The Ohio State University, 206 Rightmire Hall, 1060 Carmack Rd, Columbus, OH, 43210, USA e-mail: [email protected] M. Manto, D.L. Gruol, J.D. Schmahmann, N. Koibuchi, F. Rossi (eds.), 127 Handbook of the Cerebellum and Cerebellar Disorders, DOI 10.1007/978-94-007-1333-8_8, # Springer Science+Business Media Dordrecht 2013
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cataloging of spontaneous cerebellar mouse mutants starting in the 1950s and 1960s, surged with the availability of positional cloning and reverse genetics approaches available in the mouse in the late 1980s and 1990s, and now continues with the development of high-throughput methods for the identification of hundreds to thousands of gene expression changes resulting from single gene lesions as well as the creation of public data repositories that can be mined for structure, sequence, and expression information for all genes. The purpose of this chapter is to summarize some key cerebellar gene networks that are known to date. It is not meant to be all-inclusive, but will serve as a foundation to expand on in future editions. Consideration of the spontaneous cerebellar mutants for which the target gene or molecular mechanism has been identified is a natural starting point and organizational guide for this chapter. The kinds of genes that have been identified in this group represent most of the major developmentally important classes into which all other key cerebellar development genes can be fi
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