Ille Fabian, Atanasoski Suzana, Falk Sven, Ittner Lars M, Märki David, Büchmann-Møller Stine, Wurdak Heiko, Suter Ueli, Taketo Makoto M, Sommer Lukas
Institute of Cell Biology, ETH Zurich, 8093 Zürich, Switzerland.
Dev Biol. 2007 Apr 1;304(1):394-408. doi: 10.1016/j.ydbio.2006.12.045. Epub 2006 Dec 23.
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 Wnt signaling promotes cell cycle progression in stem and progenitor cells. However, overexpression of Wnt factors or, as shown here, stabilization of the Wnt 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, Wnt 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 Wnt in spinal cord neuroepithelial cells. Conversely, Wnt antagonizes BMP-dependent neuronal differentiation. Thus, a mutually inhibitory crosstalk between Wnt 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.
在中枢神经系统（CNS）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）的背侧信号主要作为一种模式信号，而经典Wnt信号促进干细胞和祖细胞的细胞周期进程。然而，Wnt因子的过表达，或者如本文所示，Wnt信号成分β-连环蛋白的稳定化，在脊髓腹侧比背侧具有更显著的作用，揭示了信号解读的局部差异。有趣的是，Wnt信号与脊髓背侧的BMP信号激活相关。这表明这些通路之间存在空间上受限的相互作用。实际上，BMP抵消了Wnt在脊髓神经上皮细胞中促进的增殖。相反，Wnt拮抗BMP依赖的神经元分化。因此，Wnt和BMP信号之间相互抑制的串扰控制着增殖和分化之间的平衡。由此出现了一个模型，其中背侧Wnt/BMP信号整合将生长和模式形成联系起来，从而维持形成发育中脊髓背侧边界的未分化和慢循环神经祖细胞。
