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出生后小鼠胼胝体发育过程中的蛋白质组动态变化。

Proteome dynamics during postnatal mouse corpus callosum development.

机构信息

Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.

Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.

出版信息

Sci Rep. 2017 Mar 28;7:45359. doi: 10.1038/srep45359.

Abstract

Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled amino acids in mammals (SILAM). The analyzed corpus callosi had distinct proteomic profiles depending on age, indicating rapid progression of specific molecular events during this period. The proteomic profiles were then segregated into five separate clusters, each with distinct trajectories relevant to their intended developmental functions. Our analysis both confirms many previously-identified proteins in aspects of corpus callosum development, and identifies new candidates in understudied areas of development including callosal axon refinement. We present a valuable resource for identifying new proteins integral to corpus callosum development that will provide new insights into the development and diseases afflicting this structure.

摘要

皮质连接的形成需要许多离散阶段的精确协调。这在胼胝体的发育中尤为重要,其发育经历了几个动态阶段,包括轴突投射的交叉、多余投射的消除以及已建立的束的髓鞘形成。为了全面描述这个动态过程中的分子事件,我们着手确定调节胼胝体形成的蛋白质的独特时空表达及其各自的发育功能。我们对早期(postnatal)的新生小鼠胼胝体进行了基于质谱的蛋白质组学分析,此前对其的研究证据有限,我们使用了哺乳动物稳定同位素标记的氨基酸(SILAM)。分析后的胼胝体根据年龄具有不同的蛋白质组学特征,表明在这一时期特定分子事件的快速进展。然后,蛋白质组学图谱被分为五个单独的簇,每个簇都有与其预期发育功能相关的独特轨迹。我们的分析既证实了胼胝体发育方面的许多先前鉴定的蛋白质,也确定了在发育的研究较少的领域中的新候选蛋白,包括胼胝体轴突细化。我们为鉴定对胼胝体发育至关重要的新蛋白质提供了有价值的资源,这将为理解影响该结构的发育和疾病提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/702f/5368975/b3f930d32140/srep45359-f1.jpg

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