School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
J Comp Neurol. 2011 Dec 1;519(17):3532-48. doi: 10.1002/cne.22721.
Development of the cerebellum involves the coordinated proliferation, differentiation, maturation, and integration of cells from multiple neuronal and glial lineages. In rodent models, much of this occurs in the early postnatal period. However, our understanding of the molecular mechanisms that regulate this phase of cerebellar development remains incomplete. Here, we address the role of the transcription factor nuclear factor one X (NFIX), in postnatal development of the cerebellum. NFIX is expressed by progenitor cells within the external granular layer and by cerebellar granule neurons within the internal granule layer. Using NFIX⁻/⁻ mice, we demonstrate that the development of cerebellar granule neurons and Purkinje cells within the postnatal cerebellum is delayed in the absence of this transcription factor. Furthermore, the differentiation of mature glia within the cerebellum, such as Bergmann glia, is also significantly delayed in the absence of NFIX. Collectively, the expression pattern of NFIX, coupled with the delays in the differentiation of multiple cell populations of the developing cerebellum in NFIX⁻/⁻ mice, suggest a central role for NFIX in the regulation of cerebellar development, highlighting the importance of this gene for the maturation of this key structure.
小脑的发育涉及来自多个神经元和神经胶质谱系的细胞的协调增殖、分化、成熟和整合。在啮齿动物模型中,大部分发生在出生后的早期阶段。然而,我们对调节小脑发育这一阶段的分子机制的理解仍然不完整。在这里,我们研究了转录因子核因子之一 X (NFIX) 在小脑发育后期的作用。NFIX 由外颗粒层中的祖细胞和内颗粒层中的小脑颗粒神经元表达。使用 NFIX⁻/⁻ 小鼠,我们证明在没有这种转录因子的情况下,小脑颗粒神经元和浦肯野细胞在后脑的发育会延迟。此外,成熟的神经胶质细胞(如伯格曼胶质细胞)在 NFIX 缺失的情况下分化也显著延迟。总的来说,NFIX 的表达模式,以及 NFIX⁻/⁻ 小鼠中发育中的小脑多个细胞群体的分化延迟,表明 NFIX 在调节小脑发育中起着核心作用,突出了该基因对这个关键结构成熟的重要性。