Regeneration of Drosophila sensory neuron axons and dendrites is regulated by the Akt pathway involving Pten and microRNA bantam
Regeneration of Drosophila sensory neuron axons and dendrites is regulated by the Akt pathway involving Pten and microRNA bantam
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DOI：
10.1101/gad.193243.112
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发表时间：
2012-07-15
影响因子：
10.5
通讯作者：
Jan, Yuh Nung
中科院分区：
文献类型：
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作者：
Song, Yuanquan;Ori-McKenney, Kassandra M.;Jan, Yuh Nung
细胞内源性和外源性途径都控制着轴突再生，但只有有限数量的因素被确定，并且不清楚轴突再生在多大程度上是进化保守的。树突是否也能再生尚不清楚。本研究发现，与哺乳动物感觉神经元的轴突一样，果蝇树突状树突（da）神经元的轴突能够在外周而非中枢神经系统中大量再生，激活Akt通路可增强中枢神经系统的轴突再生。此外，那些能够轴突再生的da神经元也表现出树突再生，这是细胞类型特异性的，发育调节的，并与微管极性反转有关。上皮细胞来源的microRNA bantam通过抑制Akt通路抑制da神经元中的树突再生，但通过细胞自主激活Akt通路促进树突再生。我们的研究开始揭示树突再生的机制，这取决于外在和内在因素，包括PTEN-Akt通路，它对轴突再生也很重要。因此，我们建立了一个重要的新模型系统——类似于哺乳动物损伤模型的果蝇神经元再生模型，以此来研究和获得对再生机制的新见解。
Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified and it is not clear to what extent axon regeneration is evolutionarily conserved. Whether dendrites also regenerate is unknown. Here we report that, like the axons of mammalian sensory neurons, the axons of certain Drosophila dendritic arborization (da) neurons are capable of substantial regeneration in the periphery but not in the CNS, and activating the Akt pathway enhances axon regeneration in the CNS. Moreover, those da neurons capable of axon regeneration also display dendrite regeneration, which is cell type-specific, developmentally regulated, and associated with microtubule polarity reversal. Dendrite regeneration is restrained via inhibition of the Akt pathway in da neurons by the epithelial cell-derived microRNA bantam but is facilitated by cell-autonomous activation of the Akt pathway. Our study begins to reveal mechanisms for dendrite regeneration, which depends on both extrinsic and intrinsic factors, including the PTEN-Akt pathway that is also important for axon regeneration. We thus established an important new model system-the fly da neuron regeneration model that resembles the mammalian injury model-with which to study and gain novel insights into the regeneration machinery.