Abstract:
The well-organized cerebellar structures and neuronal networks are likely crucial for their functions in motor coordination, motor learning, cognition, and emotion. Such cerebellar structures and neuronal networks are formed during developmental periods through orchestrated mechanisms, which include not only cell-autonomous programs but also interactions between the same or different types of neurons. Cerebellar granule cells (GCs) are the most numerous neurons in the brain and are generated through intensive cell division of GC precursors (GCPs) during postnatal developmental periods. While GCs go through their own developmental processes of proliferation, differentiation, migration, and maturation, they also play a crucial role in cerebellar development. One of the best-characterized contributions is the enlargement and foliation of the cerebellum through massive proliferation of GCPs. In addition to this contribution, studies have shown that immature GCs and GCPs regulate multiple factors in the developing cerebellum, such as the development of other types of cerebellar neurons or the establishment of afferent innervations. These studies have often found impairments of cerebellar development in animals lacking expression of certain molecules in GCs, suggesting that the regulations are mediated by molecules that are secreted from or present in GCs. Given the growing recognition of GCs as regulators of cerebellar development, this review will summarize our current understanding of cerebellar development regulated by GCs and molecules in GCs, based on accumulated studies and recent findings, and will discuss their potential further contributions.
摘要:
组织良好的小脑结构和神经元网络可能对它们在运动协调中的功能至关重要,运动学习,认知,和情感。这种小脑结构和神经元网络是在发育期通过协调机制形成的,其中不仅包括细胞自主程序,还包括相同或不同类型神经元之间的相互作用。小脑颗粒细胞(GC)是大脑中数量最多的神经元,是在出生后发育期通过GC前体(GCP)的密集细胞分裂产生的。当GC经历自己的增殖发展过程时,分化,迁移,和成熟,它们在小脑发育中也起着至关重要的作用。最典型的贡献之一是通过GCP的大量增殖使小脑扩大和脱落。除了这一贡献,研究表明,未成熟的GCs和GCP调节发育小脑中的多种因素,例如其他类型的小脑神经元的发育或传入神经支配的建立。这些研究经常发现在GCs中缺乏某些分子表达的动物中小脑发育受损,这表明这些调节是由GCs分泌或存在于GCs中的分子介导的。鉴于人们越来越认识到GC是小脑发育的调节因子,这篇综述将总结我们目前对GCs和GCs中分子调节的小脑发育的理解,根据积累的研究和最近的发现,并将讨论他们潜在的进一步贡献。