Boundary Formation through a Direct Threshold-Based Readout of Mobile Small RNA Gradients

Small RNAs have emerged as a new class of mobile signals. Here, we investigate their mechanism of action and show that mobile small RNAs generate sharply defined domains of target gene expression through an intrinsic and direct threshold-based readout of their mobility gradients. This readout is highly sensitive to small RNA levels at the source, allowing plasticity in the positioning of a target gene expression boundary. Besides patterning their immediate targets, the readouts of opposing small RNA gradients enable specification of robust, uniformly positioned developmental boundaries. These patterning properties of small RNAs are reminiscent of those of animal morphogens. However, their mode of action and the intrinsic nature of their gradients distinguish mobile small RNAs from classical morphogens and present a unique direct mechanism through which to relay positional information. Mobile small RNAs and their targets thus emerge as highly portable, evolutionarily tractable regulatory modules through which to create pattern. [Display omitted] •Mobile small RNAs generate sharply defined domains of target gene expression•Small RNA-to-target ratio instructs the threshold-based readout of mobility gradients•Mobile small RNAs present a unique direct mechanism to relay positional information•Readouts of opposing small RNA gradients specify robust developmental boundaries Skopelitis et al. show that mobile small RNAs act as morphogens in development, generating sharp gene expression boundaries through an intrinsic and direct threshold-based readout of their mobility gradients. The findings highlight a distinctive patterning mechanism that generates flexibly positioned yet robust developmental boundaries.