Steroid Hormone Ecdysone Signaling Specifies Mushroom Body Neuron Sequential Fate via Chinmo

Steroid Hormone Ecdysone Signaling Specifies Mushroom Body Neuron Sequential Fate via Chinmo
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类固醇激素蜕皮激素信号通过 Chinmo 指定蘑菇体神经元的顺序命运

DOI:
10.1016/j.cub.2017.08.037
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发表时间:
2017
期刊:
影响因子:
9.2
通讯作者:
G. Tavosanis
G. Tavosanis
中科院分区:
生物学1区
文献类型:
--
作者:
Giovanni Marchetti;G. Tavosanis

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成人大脑神经元组成的功能变化是在发育过程中确立的。最近的研究表明,遗传内在程序和外部线索之间的相互作用对于产生适当的神经多样性是必要的[1]。然而,这种发育过程背后的分子机制仍然知之甚少。果蝇蘑菇体(MB)神经元的三个主要亚型在发育过程中依次产生,为发育中的神经可塑性提供了一个很好的例子[2]。我们目前的数据表明,环境控制的类固醇激素蜕皮激素在幼虫-幼虫转变过程中对早期出生的MB神经元的命运起着调节作用。我们发现BTB-锌指因子Chinmo作用于蜕皮激素信号的上游,促进神经元命运的切换。事实上,Chinmo调节蜕皮激素受体B1亚型的表达,以调节γ和α‘β’MB神经元的产生。此外,我们为调控负反馈环路驱动α‘β’到αβMB神经元的转变提供了遗传学证据,在该环路中,蜕皮激素信号转而控制着microRNAlet-7对Chinmo表达的抑制。因此,我们的结果揭示了MB神经指定通路中的一种新的相互作用,通过外部激素信号和内在转录因子级联之间的相互作用来暂时控制神经元的特性。
The functional variety in neuronal composition of an adult brain is established during development. Recent studies proposed that interactions between genetic intrinsic programs and external cues are necessary to generate proper neural diversity [1]. However, the molecular mechanisms underlying this developmental process are still poorly understood. Three main subtypes ofDrosophilamushroom body (MB) neurons are sequentially generated during development and provide a good example of developmental neural plasticity [2]. Our present data propose that the environmentally controlled steroid hormone ecdysone functions as a regulator of early-born MB neuron fate during larval-pupal transition. We found that the BTB-zinc finger factor Chinmo acts upstream of ecdysone signaling to promote a neuronal fate switch. Indeed, Chinmo regulates the expression of the ecdysone receptor B1 isoform to mediate the production of γ and α′β′ MB neurons. In addition, we provide genetic evidence for a regulatory negative feedback loop driving the α′β′ to αβ MB neuron transition in which ecdysone signaling in turn controls microRNAlet-7depression of Chinmo expression. Thus, our results uncover a novel interaction in the MB neural specification pathway for temporal control of neuronal identity by interplay between an extrinsic hormonal signal and an intrinsic transcription factor cascade.
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