Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord
Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord
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DOI：
10.1016/j.ydbio.2006.12.045
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发表时间：
2007-04-01
影响因子：
2.7
通讯作者：
Sommer, Lukas
中科院分区：
文献类型：
--
作者：
Ille, Fabian;Atanasoski, Suzana;Sommer, Lukas
在中枢神经系统（CNS）的早期发育过程中，多种信号通路调节神经祖细胞的增殖和分化。在脊髓中，骨形态发生蛋白 (BMP) 的背侧信号主要充当模式信号，而规范的 Writ 信号则促进干细胞和祖细胞的细胞周期进程。然而，令状因子的过度表达，或者如此处所示，令状信号成分β-连环蛋白的稳定性在腹侧脊髓中比在背侧脊髓中具有更显着的影响，揭示了信号解释的局部差异。有趣的是，Writ 信号传导与背侧脊髓中的 BMP 信号激活相关。这表明这些路径之间的相互作用在空间上受到限制。事实上，BMP 可以抵消 Writ 在脊髓神经上皮细胞中促进的增殖。相反，Writ 会拮抗 BMP 依赖性神经元分化。因此，Writ 和 BMP 信号之间的相互抑制串扰控制着增殖和分化之间的平衡。出现了一种模型，其中背侧 Wnt/BMP 信号整合将生长和模式联系起来，从而维持形成发育中脊髓的背侧界限的未分化和缓慢循环的神经祖细胞。 (c) 2006 Elsevier Inc. 保留所有权利。
Multiple signaling pathways regulate proliferation and differentiation of neural progenitor cells during early development of the central nervous system (CNS). In the spinal cord, dorsal signaling by bone morphogenic protein (BMP) acts primarily as a patterning signal, while canonical Writ signaling promotes cell cycle progression in stem and progenitor cells. However, overexpression of Writ factors or, as shown here, stabilization of the Writ signaling component beta-catenin has a more prominent effect in the ventral than in the dorsal spinal cord, revealing local differences in signal interpretation. Intriguingly, Writ signaling is associated with BMP signal activation in the dorsal spinal cord. This points to a spatially restricted interaction between these pathways. Indeed, BMP counteracts proliferation promoted by Writ in spinal cord neuroepithelial cells. Conversely, Writ antagonizes BMP-dependent neuronal differentiation. Thus, a mutually inhibitory crosstalk between Writ and BMP signaling controls the balance between proliferation and differentiation. A model emerges in which dorsal Wnt/BMP signal integration links growth and patterning, thereby maintaining undifferentiated and slow-cycling neural progenitors that form the dorsal confines of the developing spinal cord. (c) 2006 Elsevier Inc. All rights reserved.