树突状结构的精确发展是成熟神经元电路的关键决定因素。microRNA(miRNA)介导的蛋白质合成调控在树突形态发生中起着至关重要的作用,但miRNA诱导的沉默复合物(miRISC)蛋白组分在这一过程中的作用研究较少。这里,我们展示了关键miRISC蛋白的重要作用,GW182模拟TNRC6A,在树突生长的调节中。我们确定了大鼠出生后发育过程中GW182的独特脑区域特异性时空表达模式。我们发现GW182表达峰的窗口与广泛的树突生长时期一致,海马体和小脑.在特定的时间窗口期间GW182功能的扰动导致培养的海马神经元的树突生长减少。机械上,我们表明GW182通过调节发育神经元的整体体树突翻译和肌动蛋白细胞骨架动力学来调节树突生长。此外,我们发现GW182通过调节肌动蛋白调节剂LIMK1的表达影响树突状结构。一起来看,我们的数据揭示了先前未描述的GW182的神经发育表达模式及其在树突形态发生中的作用,涉及翻译控制和肌动蛋白细胞骨架重排。本文与该论文的第一作者进行了相关的第一人称访谈。
Precise development of the dendritic architecture is a critical determinant of mature neuronal circuitry. MicroRNA (miRNA)-mediated regulation of protein synthesis plays a crucial role in dendritic morphogenesis, but the role of miRNA-induced silencing complex (miRISC) protein components in this process is less studied. Here, we show an important role of a key miRISC protein, the
GW182 paralog TNRC6A, in the regulation of dendritic growth. We identified a distinct brain region-specific spatiotemporal expression pattern of
GW182 during rat postnatal development. We found that the window of peak
GW182 expression coincides with the period of extensive dendritic growth, both in the hippocampus and cerebellum. Perturbation of
GW182 function during a specific temporal window resulted in reduced dendritic growth of cultured hippocampal neurons. Mechanistically, we show that GW182 modulates dendritic growth by regulating global somatodendritic translation and actin cytoskeletal dynamics of developing neurons. Furthermore, we found that
GW182 affects dendritic architecture by regulating the expression of actin modulator LIMK1. Taken together, our data reveal a previously undescribed neurodevelopmental expression pattern of GW182 and its role in dendritic morphogenesis, which involves both translational control and actin cytoskeletal rearrangement. This article has an associated First Person interview with the first author of the paper.