Title
Small Regulatory Rnas May Sharpen Spatial Expression Patterns
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.
Year
DOI
Venue
2007
10.1371/journal.pcbi.0030233
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
nuclear proteins,embryos,hox genes,microrna,gene targeting,transcription factors,morphogenesis
Morphogen,Gene targeting,Gene,Biology,microRNA,Gene expression,Hox gene,Messenger RNA,Bioinformatics,Genetics,Transcription factor
Journal
Volume
Issue
ISSN
3
11
1553-734X
Citations 
PageRank 
References 
6
1.97
2
Authors
3
Name
Order
Citations
PageRank
Erel Levine111919.50
Peter McHale262.30
Herbert Levine38212.58