Developmental expression of Wnt signaling factors in mouse brain
Developmental expression of Wnt signaling factors in mouse brain
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DOI：
10.4161/cbt.313
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发表时间：
2002-11-01
影响因子：
3.6
通讯作者：
Amini, S
中科院分区：
文献类型：
--
作者：
Coyle-Rink, J;Del Valle, L;Amini, S
Writ信号通路与多种诱导神经发生的生物事件有关。在这项研究中，我们的目的是研究Wnt途径的各种组分，包括β -连环蛋白及其伙伴LEF-1 /TCF-4、GSK-30及其核靶基因c-myc和cyclin D1在小鼠大脑发育过程中的表达模式。我们对大脑皮层、脑干和小脑进行了一系列的Western blot和免疫组织化学检测，发现这些蛋白在不同发育阶段的不同类型的脑细胞（包括神经元、星形胶质细胞和少突胶质细胞）中积累的差异。随着大脑的发育，5天大的皮层和脑干神经元中β -连环蛋白的细胞质免疫标记显著减少，而磷酸化β -连环蛋白并导致其不稳定的GSK-30的水平在大脑成熟过程中增加。另一方面，大脑发育早期神经元和星形胶质细胞中高水平积累的LEF-1和TCF-4在后期逐渐减少。有趣的是，虽然在神经元细胞质中检测到大部分LEF-1和TCF-4的免疫反应性，但很明显这两种蛋白都在星形胶质细胞的细胞核中积累。细胞周期蛋白D1是一种控制细胞周期和增殖的蛋白质，在发育过程中，在整个脑实质的星形胶质细胞细胞核中显示出强烈的染色。有趣的是，在大脑发育过程中，在皮层、脑干和小脑的神经元细胞质中发现了周期蛋白D。这些数据为Wnt信号通路在大脑发育过程中的差异表达提供了令人信服的证据，并表明这些信号通路在不同的大脑区域和细胞类型中可能具有不同的功能。
The Writ signaling pathway has been implicated in a variety of biological events inducing neurogenesis. In this study, we aim to investigate the expression pattern of various components of the Wnt pathway including beta-catenin and its partners LEF-1 /TCF-4, GSK-30 and their nuclear target genes such as c-myc and cyclin D1 during mouse brain development. We performed a series of Western blot and immunohistochemistry of brain cortex, brainstem, and cerebellum which revealed differential accumulation of these proteins in different types of brain cells including neurons, astrocytes, and oligodendrocytes at different developmental stages. Intense cytoplasmic immunolabeling of beta-catenin in 5 day old neurons throughout the cortex and brainstem significantly decreased as the brain developed, whereas the level of GSK-30, the protein that phosphorylates beta-catenin and causes its destabilization, increased during brain maturation. On the other hand, high level accumulation of LEF-1 and TCF-4 in neurons and astrocytes at the early stage of brain development diminished at the later stages. Interestingly, while the majority of LEF-1 and TCF-4 immunoreactivity was detected in the cytoplasm of neurons, it was evident that both proteins accumulated in the nuclei of astrocytes. Examination of cyclin D1, a protein that controls the cell cycle and proliferation, exhibited an intense staining in the nuclei of astrocytes throughout brain parenchyma during development. Interestingly, cyclin D was found in the cytoplasm of neurons from cortex, brainstem, and cerebellum during brain development. These data provide compelling evidence for the differential expression of the Wnt signaling pathway during brain development, and suggest that these signaling pathways may function differently in various brain regions and cell types.