Savill Rebecca M, Scotting Paul J, Coyle Beth
Children's Brain Tumour Research Centre, Institute of Genetics, School of Biology, University of Nottingham, UK.
Cerebellum. 2005;4(4):271-8. doi: 10.1080/14734220500367790.
Studying gene expression in granule cells is a major route to understanding the factors required for many key cellular processes such as specification, proliferation, migration, differentiation, apoptosis, tumour formation and neurodegeneration. A greater understanding of these processes will not only provide insight into cerebellum development, but also diseases of the cerebellum. Granule cells can be readily grown in culture and both viral and non-viral strategies have been optimised to allow gene transfer and expression in cultured cells. However, granule cell migration and maturation are inherent parts of cerebellum development and these rely on interactions with other cells. Hence, a true picture of gene function in these cells can only be obtained when tissue context is maintained. Studies of gene function in this context can be achieved by creation of mouse models. Conditional mouse models, where loss of gene expression is restricted as far as possible to granule cells, are by far the most informative resource in this respect. Despite their obvious benefits, the production of mouse models is both costly and time-consuming and this may be further compounded by a potential lack of phenotype due to redundancy of gene function. Organotypic slice cultures, on the other hand, are a comparatively cheap and accessible model for studies of gene function where tissue context is maintained. Recent technologies have provided the means to manipulate gene expression in such systems and are beginning to yield valuable insights into the molecular regulation of cerebellum development.
研究颗粒细胞中的基因表达是理解许多关键细胞过程所需因素的主要途径，这些过程包括细胞特化、增殖、迁移、分化、凋亡、肿瘤形成和神经退行性变。对这些过程的更深入理解不仅将有助于深入了解小脑发育，还能帮助了解小脑疾病。颗粒细胞能够在培养物中轻松生长，并且病毒和非病毒策略均已得到优化，以实现基因在培养细胞中的转移和表达。然而，颗粒细胞的迁移和成熟是小脑发育的固有组成部分，这些过程依赖于与其他细胞的相互作用。因此，只有在维持组织环境的情况下，才能获得这些细胞中基因功能的真实情况。在这种情况下，可以通过创建小鼠模型来研究基因功能。条件性小鼠模型是目前这方面信息最丰富的资源，在该模型中，基因表达的缺失尽可能局限于颗粒细胞。尽管小鼠模型有明显的优势，但生产小鼠模型既昂贵又耗时，而且由于基因功能冗余可能导致潜在的表型缺失，这可能会使情况更加复杂。另一方面，器官型切片培养是一种相对便宜且易于获得的模型，用于在维持组织环境的情况下研究基因功能。最近的技术提供了在这类系统中操纵基因表达的方法，并开始对小脑发育的分子调控产生有价值的见解。
