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Peter McHale

Publications and source records attributed to Peter McHale.

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microRNAs may sharpen spatial expression patterns

The precise layout of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low expression domains requires a genetic mechanism which is both sensitive and 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. While 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 where small RNAs interact with a target gene and diffusively move from cell to cell. Though diffusion generally smears 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. We discuss the applicability of our results, as examples, to the case of leaf polarity establishment in maize and Hox patterning in the early {\it 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.

q-bio.MN

Embryonic Pattern Scaling Achieved by Oppositely Directed Morphogen Gradients

Morphogens are proteins, often produced in a localised region, whose concentrations spatially demarcate regions of differing gene expression in developing embryos. The boundaries of expression must be set accurately and in proportion to the size of the one-dimensional developing field; this cannot be accomplished by a single gradient. Here, we show how a pair of morphogens produced at opposite ends of a developing field can solve the pattern-scaling problem. In the most promising scenario, the morphogens effectively interact according to the annihilation reaction $A+B\to\emptyset$ and the switch occurs according to the absolute concentration of $A$ or $B$. In this case embryonic markers across the entire developing field scale approximately with system size; this cannot be achieved with a pair of non-interacting gradients that combinatorially regulate downstream genes. This scaling occurs in a window of developing-field sizes centred at a few times the morphogen decay length.

q-bio.SC