Abstract
The precise establishment of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low spatial expression domains requires a genetic mechanism that exhibits sensitivity, yet is robust to fluctuations, a demand that may not be easily achieved by morphogens alone. Recently, it has been demonstrated that small RNAs (and, in particular, microRNAs) play many roles in embryonic development. Whereas some RNAs are essential for embryogenesis, others are limited to fine-tuning a predetermined gene expression pattern. Here, we explore the possibility that small RNAs participate in sharpening a gene expression profile that was crudely established by a morphogen. To this end, we study a model in which small RNAs interact with a target gene and diffusively move from cell to cell. Though diffusion generally smoothens spatial expression patterns, we find that intercellular mobility of small RNAs is actually critical in sharpening the interface between target expression domains in a robust manner. This sharpening occurs as small RNAs diffuse into regions of low mRNA expression and eliminate target molecules therein, but cannot affect regions of high mRNA levels. We discuss the applicability of our results, as examples, to the case of leaf polarity establishment in maize and Hox patterning in the early Drosophila embryo. Our findings point out the functional significance of some mechanistic properties, such as mobility of small RNAs and the irreversibility of their interactions. These properties are yet to be established directly for most classes of small RNAs. An indirect yet simple experimental test of the proposed mechanism is suggested in some detail.
Highlights
Morphogenesis proceeds by sequential divisions of a developing embryo into domains, each expressing a distinct set of genes
It has been suggested that small RNA molecules, such as microRNAs, may play a role in establishing a sharp boundary between two neighboring segments, but are not required for the overall patterning
We find that mobility of the small RNAs may generate a sharp interface in the expression profile of its target gene
Summary
Morphogenesis proceeds by sequential divisions of a developing embryo into domains, each expressing a distinct set of genes. Two adjacent domains may be differentiated by high expression of some genes in one, and low expression in the other. In such cases, it is important that cells of the two populations do not intermix. The number of cells that show intermediate levels of expression, typically found at the interface between the two sets, should be kept to a minimum. These demands are necessary in order to unambiguously define the identity of each cell. A spatial gene expression pattern that obeys these demands is said to exhibit a sharp interface
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