A framework for understanding the roles of miRNAs in animal development.

Abstract

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.