Journal
FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2014.00450
Keywords
cerebellum structure; apoptosis; autophagy; brain development; epigenetics; DNA methylation; aging
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Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC) [341921-2012, 372405-2009]
- FHS Bridge Funding of Highly Ranked CIHR Open Operating Grants
- University of Manitoba start up grant
- Canadian Institutes of Health Research Team Grant [TEC-128094]
- Health Sciences Center Foundation (HSCF)
- CIHR Catalyst Grant [CEN-132383]
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The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in similar to 5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum.
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