Alberti Chiara, Cochella Luisa
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), 1030 Vienna, Austria
Development. 2017 Jul 15;144(14):2548-2559. doi: 10.1242/dev.146613.
MicroRNAs (miRNAs) contribute to the progressive changes in gene expression that occur during development. The combined loss of all miRNAs results in embryonic lethality in all animals analyzed, illustrating the crucial role that miRNAs play collectively. However, although the loss of some individual miRNAs also results in severe developmental defects, the roles of many other miRNAs have been challenging to uncover. This has been mostly attributed to their proposed function as tuners of gene expression or providers of robustness. Here, we present a view of miRNAs in the context of development as a hierarchical and canalized series of gene regulatory networks. In this scheme, only a fraction of embryonic miRNAs act at the top of this hierarchy, with their loss resulting in broad developmental defects, whereas most other miRNAs are expressed with high cellular specificity and play roles at the periphery of development, affecting the terminal features of specialized cells. This view could help to shed new light on our understanding of miRNA function in development, disease and evolution.
微小RNA（miRNA）促成了发育过程中发生的基因表达的渐进性变化。在所有被分析的动物中，所有miRNA的共同缺失都会导致胚胎致死，这说明了miRNA共同发挥的关键作用。然而，尽管一些单个miRNA的缺失也会导致严重的发育缺陷，但许多其他miRNA的作用却难以揭示。这主要归因于它们被认为具有作为基因表达调节者或稳健性提供者的功能。在这里，我们提出了一种观点，即在发育过程中，miRNA是一系列分层且受限的基因调控网络。在这个模式中，只有一小部分胚胎期miRNA在这个层级的顶端起作用，它们的缺失会导致广泛的发育缺陷，而大多数其他miRNA以高度的细胞特异性表达，并在发育的外围发挥作用，影响特化细胞的终末特征。这种观点可能有助于为我们理解miRNA在发育、疾病和进化中的功能提供新的思路。
