Max-Planck Institute of Neurobiology, Sensory Neurogenetics Research Group, 82152 Martinsried, Germany.
J Neurosci. 2011 Nov 2;31(44):15660-73. doi: 10.1523/JNEUROSCI.2592-11.2011.
CO(2) sensation represents an interesting example of nervous system and behavioral evolutionary divergence. The underlying molecular mechanisms, however, are not understood. Loss of microRNA-279 in Drosophila melanogaster leads to the formation of a CO(2) sensory system partly similar to the one of mosquitoes. Here, we show that a novel allele of the pleiotropic transcription factor Prospero resembles the miR-279 phenotype. We use a combination of genetics and in vitro and in vivo analysis to demonstrate that Pros participates in the regulation of miR-279 expression, and that reexpression of miR-279 rescues the pros CO(2) neuron phenotype. We identify common target molecules of miR-279 and Pros in bioinformatics analysis, and show that overexpression of the transcription factors Nerfin-1 and Escargot (Esg) is sufficient to induce formation of CO(2) neurons on maxillary palps. Our results suggest that Prospero restricts CO(2) neuron formation indirectly via miR-279 and directly by repressing the shared target molecules, Nerfin-1 and Esg, during olfactory system development. Given the important role of Pros in differentiation of the nervous system, we anticipate that miR-mediated signal tuning represents a powerful method for olfactory sensory system diversification during evolution.
CO(2) 感觉代表了神经系统和行为进化分歧的一个有趣例子。然而，其潜在的分子机制尚不清楚。果蝇中 microRNA-279 的缺失会导致形成部分类似于蚊子的 CO(2) 感觉系统。在这里，我们表明多效性转录因子 Prospero 的一个新等位基因类似于 miR-279 表型。我们使用遗传学以及体外和体内分析的组合来证明 Pros 参与 miR-279 表达的调节，并且 miR-279 的重新表达挽救了 pros CO(2) 神经元表型。我们在生物信息学分析中确定了 miR-279 和 Pros 的常见靶分子，并表明转录因子 Nerfin-1 和 Escargot (Esg) 的过表达足以诱导上颌触须上 CO(2) 神经元的形成。我们的结果表明，Prospero 通过 miR-279 间接限制 CO(2) 神经元的形成，并通过直接抑制共享靶分子 Nerfin-1 和 Esg 来抑制 CO(2) 神经元的形成嗅觉系统发育。鉴于 Pros 在神经系统分化中的重要作用，我们预计 miR 介导的信号调谐代表了在进化过程中嗅觉感觉系统多样化的一种强大方法。
