The Formation of the Bicoid Morphogen Gradient Requires Protein Movement from Anteriorly Localized mRNA

Shawn C Little,Eric F Wieschaus,Gašper Tkačik,Thomas Gregor,Thomas B Kneeland,Claude Desplan

doi:10.1371/journal.pbio.1000596

Shawn C Little, Eric F Wieschaus + Show 4 more

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https://doi.org/10.1371/journal.pbio.1000596

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Abstract

Author SummaryThe Bicoid protein gradient plays a crucial role in determining the anterior body pattern of Drosophila embryos. This gradient is the classic example of morphogen-mediated patterning of a developing metazoan and serves as a major topic for mathematical modeling. Accurate modeling of the gradient requires a detailed account of the underlying bicoid mRNA distribution. The classic model holds that mRNA protein gradient arises via protein diffusion from mRNA localized at the anterior of the developing egg. In contrast, recent proposals suggest that an mRNA gradient generates the protein gradient without protein movement. In this study, we introduce a novel mRNA quantification method for Drosophila embryos, which allows us to visualize each individual mRNA particle accurately in whole embryos. We demonstrate that all but a few mRNA particles are confined to the anterior 20% of the egg, and consequently that the protein must move in order to establish a gradient. We further report that the mRNA distribution is highly dynamic during the time of protein synthesis. In numerical simulations, we show that incorporating realistic spatial locations of the individual source mRNA molecules throughout the developmental period is necessary to accurately model the experimentally observed protein gradient dynamics.

Highlights

Accurate development of metazoan embryos requires precise production, reception, and interpretation of patterning cues along appropriate spatial axes on realistic timescales
The classic model holds that messenger ribonucleic acid (mRNA) protein gradient arises via protein diffusion from mRNA localized at the anterior of the developing egg
We introduce a novel mRNA quantification method for Drosophila embryos, which allows us to visualize each individual mRNA particle accurately in whole embryos

Summary

Introduction

Accurate development of metazoan embryos requires precise production, reception, and interpretation of patterning cues along appropriate spatial axes on realistic timescales. Many embryonic patterning events utilize graded spatial distributions of patterning molecules, or morphogens, whose activities rely fundamentally on molecular interactions susceptible to environmental fluctuations and stochasticity in gene expression [1]. In the Drosophila embryo, anterior-posterior (AP) axial patterning originates with maternal cues deposited into the developing egg [2]. Among these cues is the transcription factor Bicoid (Bcd), the mRNA of which localizes at the anterior cortex of the oocyte [3,4,5,6]. During the blastoderm stage Bcd protein distributes along the AP axis as an exponentially decaying gradient [7,8,9], and nuclear Bcd activates target genes in a dosage-dependent manner (reviewed in [10])

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