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Epigenetics and Cerebellar Neurodevelopmental Disorders

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Development of the Cerebellum from Molecular Aspects to Diseases

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

Epigenetic mechanisms regulate cellular identity and organ morphology via controlling the gene expression program of specific cell types. Such mechanisms are not directly controlled by genomic DNA sequences and can be largely influenced by environmental factors. Epigenetic mechanisms include modification of DNA and DNA-bound proteins (histones), action of large and short regulatory RNA molecules, cross talk between DNA and histone marks, nucleosome positioning, chromatin removdeling, enhancer-promoter interactions, as well as three-dimensional chromatin structure that is in part controlled by global regulators and insulator proteins. Research on epigenetic mechanisms is an emerging hot topic today that may very well be due to the potential reversibility of epigenetic marks. Such characteristics of epigenetic modifications have brought them into the front row of research for cutting-edge therapeutic strategies. The challenge would be of course the very large number of genes that will be targeted by most epigenetic drugs that are capable of global modulation of epigenetic marks and a purposeful management of selectively targeting disease-associated genes in balance with global effects of these drugs.

Like all parts of our body, development of the central nervous system and the brain is regulated through epigenetic mechanisms. It is not of surprise that deregulation of epigenetic modifications may lead to human disease and neurodevelopmental disorders. In this book chapter, I will focus on main epigenetic mechanisms that control the brain and cerebellum development. I will then discuss some of the common neurodevelopmental disorders that have proven epigenetic components that provide important insight toward the future research on epigenetics and cerebellar neurodevelopmental disorders.

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Acknowledgment

I would like to acknowledge many other excellent research publications that are not discussed in this book chapter due to the space limitation. I would like to thank Jeff Dixon for the artwork in all figures of this book chapter. This work is supported by funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (2016-06035) and the Canadian Institute of Health Research (CIHR) Team Grant (TEC-128094). The research in my lab is supported by NSERC DG-2016-06035, CIHR-TEC-128094, International Rett Syndrome Foundation (IRSF) Basic Research Grant Award #3212, Ontario Rett Syndrome Association (ORSA), and the Children’s Research Institute of Manitoba (CHRIM). The CIHR Catalyst Grant CEN-132383 supported part of the highlighted published research from my lab on sections about Mecp2/MeCP2 regulation.

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  1. Regenerative Medicine Program, and Department of Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 745 Bannatyne Avenue, BMSB 627, Winnipeg, MB, R3E 0J9, Canada

    Mojgan Rastegar PhD

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  1. Department of Human Anatomy and Cell Science, The Children’s Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB, Canada

    Hassan Marzban

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Rastegar, M. (2017). Epigenetics and Cerebellar Neurodevelopmental Disorders. In: Marzban, H. (eds) Development of the Cerebellum from Molecular Aspects to Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-319-59749-2_10

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