Marzban Hassan, Del Bigio Marc R, Alizadeh Javad, Ghavami Saeid, Zachariah Robby M, Rastegar Mojgan
Department of Human Anatomy and Cell Science, University of Manitoba Winnipeg, MB, Canada.
Department of Human Anatomy and Cell Science, University of Manitoba Winnipeg, MB, Canada ; Department of Pathology, University of Manitoba Winnipeg, MB, Canada.
Front Cell Neurosci. 2015 Jan 12;8:450. doi: 10.3389/fncel.2014.00450. eCollection 2014.
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 ~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.
哺乳动物的小脑位于颅后窝，对运动协调以及包括认知和情感过程在内的非运动功能至关重要。小脑的解剖结构独特，具有三层皮质。在发育过程中，小脑原基细胞的神经发生和命运决定是通过涉及多个遗传途径的严格控制的分子事件精心安排的。在这篇综述中，我们将重点介绍人类和小鼠小脑的解剖结构、发育中小脑的细胞组成，以及小脑细胞命运决定所涉及的潜在基因表达程序。对细胞死亡文献的批判性评估表明，约5%的小脑细胞会发生凋亡，大多数在有丝分裂后不久。凋亡和细胞自噬可能在小脑发育中发挥重要作用，我们对它们在小脑发育和组织中的作用进行了全面讨论。我们还探讨了未折叠蛋白反应在调节小脑神经发生中的可能功能。我们讨论了在理解小脑区域的表观遗传特征以及DNA甲基化、微小RNA与小脑神经变性之间可能联系方面的最新进展。最后，我们讨论了与小脑功能障碍相关的遗传疾病及其在衰老小脑中的作用。
