The formation of the Bicoid morphogen gradient requires protein movement from anteriorly localized source Journal Article


Author(s): Little, Shawn C; Tkačik, Gašper; Kneeland, Thomas B; Wieschaus, Eric F; Gregor, Thomas
Article Title: The formation of the Bicoid morphogen gradient requires protein movement from anteriorly localized source
Affiliation IST Austria
Abstract: 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.
Journal Title: PLoS Biology
Volume: 9
Issue 3
ISSN: 1545-7885
Publisher: Public Library of Science  
Date Published: 2011-03-01
Start Page: e1000596
Copyright Statement: CC-BY
Sponsor: Princeton University, Howard Hughes Medical Institute, Searle Scholars Award 10-SSP-274, NSF grant EF-0928048, NSF grant BIO- 0928048
DOI: 10.1371/journal.pbio.1000596
Notes: We thank Saw Kyin, Michelle Lu, Reba Samanta, and Martin Scheeler for technical assistance. We thank Joe Goodhouse for confocal microscopy assistance. We thank members of the Gregor and Wieschaus labs for discussions.
Open access: yes (OA journal)