Molecular basis and function of specialized nuclear structures in mouse neurons

项目概要/摘要 小鼠神经元交替核结构的分子基础和功能 每个真核细胞都必须将其基因组折叠在细胞核内。显微镜和基因组学方法已经揭示了 哺乳动物细胞广泛共有的基因组包装和组织的常规特征。我们 实验室试图了解细胞弯曲这些规则，而不是形成不寻常的结构，实现 细胞类型的特定目的。我们先前在小鼠嗅觉感觉神经元上的工作证实了这种情况。嗅觉 感觉神经元重新组织细胞核中的DNA，使关闭的基因位于细胞核的中间。 而不是在外围。与此同时，这些细胞将嗅觉受体基因从 不同的染色体在3D空间形成专门的基因枢纽。这些中枢是嗅觉感官所独有的 神经元和管理一个关键的基因调控机制，确定这些神经元的身份，是中央 to our sense感of smell嗅觉.我们试图确定这种替代核架构是否是罕见的异常值， 它们是否比目前已知的更广泛。我们假设，替代架构可能是 在神经系统中尤其常见，在神经系统中，长寿命的有丝分裂后神经元有很长的时间来重新排列 他们的DNA，他们可能是至关重要的了解神经元如何改变对刺激的反应。我们将 开发新的方法来确定替代核结构，使我们能够确定何时何地 我们将使用来自嗅觉系统和脊髓的原代小鼠神经元来探索 这些迷人结构的功能和调节。

Project Summary/Abstract Molecular basis and function of alternative nuclear architectures in mouse neurons Every eukaryotic cell must fold its genome within its nucleus. Microscopy and genomic methods have revealed regular features of how the genome is packaged and organized that are widely shared by mammalian cells. Our lab seeks to understand cases where cells bend these rules to instead form unusual structures that achieve a cell-type specific purpose. Our prior work in mouse olfactory sensory neurons exemplifies such a case. Olfactory sensory neurons reorganize the DNA in their nucleus to that genes that are off are located in the middle of the nucleus instead of at the periphery. At the same time, these cells bring together olfactory receptor genes from different chromosomes in 3D space to form specialized gene hubs. These hubs are unique to olfactory sensory neurons and govern a critical gene regulatory mechanism that defines the identity of these neurons and is central to our sense of smell. We seek to determine whether such alternative nuclear architectures are rare outliers or whether they are more widespread than currently known. We hypothesize that alternative architectures may be particularly common in the nervous system, where long-lived post-mitotic neurons have a long time to rearrange their DNA, and that they may be critical to understanding how neurons change in response to stimuli. We will develop new ways of identifying alternative nuclear architectures that will allow us to identify when and where they form, and we will use primary mouse neurons from the olfactory system and the spinal cord to explore the function and regulation of these fascinating structures.