Dissecting the role of Wnt signaling and its interactions with FGF signaling during midbrain neurogenesis.

Neurogenesis (Austin, Tex.) Pub Date : 2015-09-21 eCollection Date: 2015-01-01 DOI:10.1080/23262133.2015.1057313
Carlene Dyer, Eric Blanc, Rob J Stanley, Robert D Knight
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引用次数: 2

Abstract

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.

Abstract Image

Abstract Image

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剖析Wnt信号在中脑神经发生中的作用及其与FGF信号的相互作用。
FGF和Wnt/ bcat信号的相互作用控制中脑发育。这种相互作用的本质以及它们如何调节模式、生长和分化尚不清楚,因为不可能暂时剖析一种途径相对于另一种途径的影响。我们使用药理学和遗传学工具来探讨FGF和Wnt在控制早期中脑神经元规范中的时间和空间作用。我们确定了GSK-3在调节FGF活性和神经元模式中的β-连环蛋白(bcat)独立作用。通过调控sprouty4,与bcat依赖的FGF信号调控重叠,使这一功能变得复杂。此外,我们揭示了Axin蛋白功能的衰减如何促进依赖于FGF活性的bcat活性水平的波动。这突出了FGF和Wnt/ bcat之间相互作用的复杂性,并揭示了它们在多个层面上相互控制中脑的活动。
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