Dissecting the role of Wnt signaling and its interactions with FGF signaling during midbrain neurogenesis.
Dissecting the role of Wnt signaling and its interactions with FGF signaling during midbrain neurogenesis.
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DOI：
10.1080/23262133.2015.1057313
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Knight RD
中科院分区：
文献类型：
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作者：
Dyer C;Blanc E;Stanley RJ;Knight RD
成纤维细胞生长因子和Wnt/BCAT信号的相互作用控制着中脑的发育。这种相互作用的性质以及它们如何调控模式、生长和分化还不太清楚，因为还不可能在时间上剖析一种途径相对于另一种途径的影响。我们使用了药理学和遗传学工具来探索成纤维细胞生长因子和Wnt在控制早期中脑神经元特化中的时空作用。我们发现GSK-3在调节成纤维细胞生长因子活性从而调节神经元构型中具有β-连环蛋白不依赖的作用。这一功能因与BCAT依赖的对成纤维细胞生长因子信号的调节重叠而变得复杂，这是通过调节芽来实现的。此外，我们揭示了Axin蛋白功能的减弱如何促进BCAT活性的波动水平，这依赖于成纤维细胞生长因子的活性。这突出了成纤维细胞生长因子和Wnt/BCAT之间相互作用的复杂性，并揭示了它们在多个水平上作用，以控制彼此在中脑的活动。
Interactions between FGF and Wnt/ bcat signaling control development of the midbrain. The nature of this interaction and how these regulate patterning, growth and differentiation is less clear, as it has not been possible to temporally dissect the effects of one pathway relative to the other. We have employed pharmacological and genetic tools to probe the temporal and spatial roles of FGF and Wnt in controlling the specification of early midbrain neurons. We identify a β-catenin (bcat) independent role for GSK-3 in modulating FGF activity and hence neuronal patterning. This function is complicated by an overlap with bcat-dependent regulation of FGF signaling, through the regulation of sprouty4. Additionally we reveal how attenuation of Axin protein function can promote fluctuating levels of bcat activity that are dependent on FGF activity. This highlights the complex nature of the interactions between FGF and Wnt/ bcat and reveals that they act at multiple levels to control each others activity in the midbrain.