Neuregulin-ErbB signaling is essential for numerous functions in the developing, adult, and aging brain, particularly in the prefrontal cortex (PFC). Mouse models with disrupted Nrg and/or ErbB genes are relevant to psychiatric, developmental, and age-related disorders, displaying a range of abnormalities stemming from cortical circuitry impairment. Many of these models display nonoverlapping phenotypes dependent upon the gene target and timing of perturbation, suggesting that cortical expression of the Nrg-ErbB network undergoes temporal regulation across the lifespan. Here, we report a comprehensive temporal expression mapping study of the Nrg-ErbB signaling network in the mouse PFC across postnatal development through aging. We find that Nrg and ErbB genes display distinct expression profiles; moreover, splice isoforms of these genes are differentially expressed across the murine lifespan. We additionally find a developmental switch in ErbB4 splice isoform expression potentially mediated through coregulation of the lncRNA Miat expression. Our results are the first to comprehensively and quantitatively map the expression patterns of the Nrg-ErbB network in the mouse PFC across the postnatal lifespan and may help disentangle the pathway's involvement in normal cortical sequences of events across the lifespan, as well as shedding light on the pathophysiological mechanisms of abnormal Nrg-ErbB signaling in neurological disease.

中文翻译：

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小鼠前额叶皮层神经调节蛋白-ErbB 网络在整个生命周期中的时间动态。

Neuregulin-ErbB 信号传导对于发育中、成人和衰老大脑中的许多功能至关重要，尤其是在前额叶皮层 (PFC) 中。Nrg 和/或 ErbB 基因被破坏的小鼠模型与精神、发育和年龄相关的疾病有关，显示出一系列由皮质电路损伤引起的异常。许多这些模型显示出非重叠表型，这取决于基因目标和扰动时间，这表明 Nrg-ErbB 网络的皮质表达在整个生命周期中都经历了时间调节。在这里，我们报告了小鼠 PFC 中 Nrg-ErbB 信号网络在出生后发育和衰老过程中的综合时间表达映射研究。我们发现 Nrg 和 ErbB 基因显示出不同的表达谱；而且，这些基因的剪接同种型在小鼠的整个生命周期中都有差异表达。我们还发现 ErbB4 剪接同种型表达的发育转换可能通过 lncRNA Miat 表达的共调节介导。我们的结果是第一个全面和定量地绘制出生后整个生命周期中小鼠 PFC 中 Nrg-ErbB 网络的表达模式的结果，并且可能有助于解开该通路在整个生命周期中参与正常皮质事件序列的过程，以及阐明Nrg-ErbB 信号异常在神经系统疾病中的病理生理机制。