Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures
Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures
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DOI：
10.1016/j.yexcr.2006.11.002
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发表时间：
2007-02-01
影响因子：
3.7
通讯作者：
Hecht, Andreas
中科院分区：
文献类型：
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作者：
Hirsch, Cordula;Campano, Louise M.;Hecht, Andreas
典型的Wnt信号传导触发由β-连环蛋白和T细胞因子组成的异二聚体转录因子复合物的形成，从而控制特定遗传程序的执行。在胚胎神经发育的扩展和神经发生阶段，经典Wnt信号最初控制神经祖细胞的增殖，以及随后的神经元分化。Wnt生长因子是否影响出生后的神经祖细胞尚不清楚。因此，我们分析了Wnt信号对从新生小鼠大脑皮层分离的神经祖细胞的影响。通路组分的表达谱显示，这些细胞完全具备响应Wnt信号的能力。然而，Wnt通路激活仅影响新生儿祖细胞的一个子集，并引起不同细胞亚群中增殖和神经元分化的有限增加。此外，Wnt通路激活仅短暂刺激S期进入，但不支持祖细胞培养物的长期增殖。Wnt反应的抑制性质与抑制途径组分的主要表达和负反馈机制的快速启动相关。有趣的是，在分化细胞培养物中，经典Wnt信号的激活降低了Hes 1和Hes 5的表达，这表明在出生后神经发育期间，Wnt/β连环蛋白信号通过干扰Notch途径活性来增强祖细胞的神经发生。(c)2006年爱思唯尔公司All rights reserved.
Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of beta-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/beta catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity. (c) 2006 Elsevier Inc. All rights reserved.