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Periodic patterning of the Drosophila eye is stabilized by the diffusible activator Scabrous.

ABSTRACT: Generation of periodic patterns is fundamental to the differentiation of multiple tissues during development. How such patterns form robustly is still unclear. The Drosophila eye comprises ?750 units, whose crystalline order is set during differentiation of the eye imaginal disc: an activation wave sweeping across the disc is coupled to lateral inhibition, sequentially selecting pro-neural cells. Using mathematical modelling, here we show that this template-based lateral inhibition is highly sensitive to spatial variations in biochemical parameters and cell sizes. We reveal the basis of this sensitivity, and suggest that it can be overcome by assuming a short-range diffusible activator. Clonal experiments identify Scabrous, a previously implicated inhibitor, as the predicted activator. Our results reveal the mechanism by which periodic patterning in the fly eye is stabilized against spatial variations, highlighting how the need to maintain robustness shapes the design of patterning circuits.

SUBMITTER: Gavish A

PROVIDER: S-EPMC4756378 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Periodic patterning of the Drosophila eye is stabilized by the diffusible activator Scabrous.

Gavish Avishai A Shwartz Arkadi A Weizman Abraham A Schejter Eyal E Shilo Ben-Zion BZ Barkai Naama N

Nature communications 20160215

Generation of periodic patterns is fundamental to the differentiation of multiple tissues during development. How such patterns form robustly is still unclear. The Drosophila eye comprises ∼750 units, whose crystalline order is set during differentiation of the eye imaginal disc: an activation wave sweeping across the disc is coupled to lateral inhibition, sequentially selecting pro-neural cells. Using mathematical modelling, here we show that this template-based lateral inhibition is highly sen ...[more]

PMID: 26876750

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Project description:Complex periodic patterns can self-organize through dynamic interactions between diffusible activators and inhibitors. In the biological context, self-organized patterning is challenged by spatial heterogeneities ('noise') inherent to biological systems. How spatial variability impacts the periodic patterning mechanism and how it can be buffered to ensure precise patterning is not well understood. We examine the effect of spatial heterogeneity on the periodic patterning of the fruit fly eye, an organ composed of ?800 miniature eye units (ommatidia) whose periodic arrangement along a hexagonal lattice self-organizes during early stages of fly development. The patterning follows a two-step process, with an initial formation of evenly spaced clusters of ?10 cells followed by a subsequent refinement of each cluster into a single selected cell. Using a probabilistic approach, we calculate the rate of patterning errors resulting from spatial heterogeneities in cell size, position and biosynthetic capacity. Notably, error rates were largely independent of the desired cluster size but followed the distributions of signaling speeds. Pre-formation of large clusters therefore greatly increases the reproducibility of the overall periodic arrangement, suggesting that the two-stage patterning process functions to guard the pattern against errors caused by spatial heterogeneities. Our results emphasize the constraints imposed on self-organized patterning mechanisms by the need to buffer stochastic effects. Author summary Complex periodic patterns are common in nature and are observed in physical, chemical and biological systems. Understanding how these patterns are generated in a precise manner is a key challenge. Biological patterns are especially intriguing, as they are generated in a noisy environment; cell position and cell size, for example, are subject to stochastic variations, as are the strengths of the chemical signals mediating cell-to-cell communication. The need to generate a precise and robust pattern in this 'noisy' environment restricts the space of patterning mechanisms that can function in the biological setting. Mathematical modeling is useful in comparing the sensitivity of different mechanisms to such variations, thereby highlighting key aspects of their design.We use mathematical modeling to study the periodic patterning of the fruit fly eye. In this system, a highly ordered lattice of differentiated cells is generated in a two-dimensional cell epithelium. The pattern is first observed by the appearance of evenly spaced clusters of ?10 cells that express specific genes. Each cluster is subsequently refined into a single cell, which initiates the formation and differentiation of a miniature eye unit, the ommatidium. We formulate a mathematical model based on the known molecular properties of the patterning mechanism, and use a probabilistic approach to calculate the errors in cluster formation and refinement resulting from stochastic cell-to-cell variations ('noise') in different quantitative parameters. This enables us to define the parameters most influencing noise sensitivity. Notably, we find that this error is roughly independent of the desired cluster size, suggesting that large clusters are beneficial for ensuring the overall reproducibility of the periodic cluster arrangement. For the stage of cluster refinement, we find that rapid communication between cells is critical for reducing error. Our work provides new insights into the constraints imposed on mechanisms generating periodic patterning in a realistic, noisy environment, and in particular, discusses the different considerations in achieving optimal design of the patterning network.

Dataset Information

Periodic patterning of the Drosophila eye is stabilized by the diffusible activator Scabrous.

Publications

Periodic patterning of the Drosophila eye is stabilized by the diffusible activator Scabrous.

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