 The Formation of the Bicoid Morphogen Gradient Requires Protein Movement from Anteriorly Localized mRNAShawn C Little, Gašper Tkačik, Thomas B Kneeland, Eric F Wieschaus and Thomas Gregor PLOS Biology, 2011, vol. 9, issue 3, 1-17 Abstract: New quantitative data show that the Bicoid morphogen gradient is generated from a dynamic localized source and that protein gradient formation requires protein movement along the anterior-posterior axis.The Bicoid morphogen gradient directs the patterning of cell fates along the anterior-posterior axis of the syncytial Drosophila embryo and serves as a paradigm of morphogen-mediated patterning. The simplest models of gradient formation rely on constant protein synthesis and diffusion from anteriorly localized source mRNA, coupled with uniform protein degradation. However, currently such models cannot account for all known gradient characteristics. Recent work has proposed that bicoid mRNA spatial distribution is sufficient to produce the observed protein gradient, minimizing the role of protein transport. Here, we adapt a novel method of fluorescent in situ hybridization to quantify the global spatio-temporal dynamics of bicoid mRNA particles. We determine that >90% of all bicoid mRNA is continuously present within the anterior 20% of the embryo. bicoid mRNA distribution along the body axis remains nearly unchanged despite dynamic mRNA translocation from the embryo core to the cortex. To evaluate the impact of mRNA distribution on protein gradient dynamics, we provide detailed quantitative measurements of nuclear Bicoid levels during the formation of the protein gradient. We find that gradient establishment begins 45 minutes after fertilization and that the gradient requires about 50 minutes to reach peak levels. In numerical simulations of gradient formation, we find that incorporating the actual bicoid mRNA distribution yields a closer prediction of the observed protein dynamics compared to modeling protein production from a point source at the anterior pole. We conclude that the spatial distribution of bicoid mRNA contributes to, but cannot account for, protein gradient formation, and therefore that protein movement, either active or passive, is required for gradient formation.Author Summary: The 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. Date: 2011 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pbio00:1000596 DOI: 10.1371/journal.pbio.1000596 Access Statistics for this article More articles in PLOS Biology from Public Library of Science |
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