title: Stable, precise, and reproducible patterning of bicoid and hunchback molecules in the early Drosophila embryo.
abstract: Precise patterning of morphogen molecules and their accurate reading out are of key importance in embryonic development. Recent experiments have visualized distributions of proteins in developing embryos and shown that the gradient of concentration of Bicoid morphogen in Drosophila embryos is established rapidly after fertilization and remains stable through syncytial mitoses. This stable Bicoid gradient is read out in a precise way to distribute Hunchback with small fluctuations in each embryo and in a reproducible way, with small embryo-to-embryo fluctuation. The mechanisms of such stable, precise, and reproducible patterning through noisy cellular processes, however, still remain mysterious. To address these issues, here we develop the one- and three-dimensional stochastic models of the early Drosophila embryo. The simulated results show that the fluctuation in expression of the hunchback gene is dominated by the random arrival of Bicoid at the hunchback enhancer. Slow diffusion of Hunchback protein, however, averages out this intense fluctuation, leading to the precise patterning of distribution of Hunchback without loss of sharpness of the boundary of its distribution. The coordinated rates of diffusion and transport of input Bicoid and output Hunchback play decisive roles in suppressing fluctuations arising from the dynamical structure change in embryos and those arising from the random diffusion of molecules, and give rise to the stable, precise, and reproducible patterning of Bicoid and Hunchback distributions.
authors.affiliation: Department of Computational Science and Engineering, Nagoya University, Nagoya, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Okabe-Oho
authors.forename: Hiroki
authors.initials: H
authors.lastname: Murakami
authors.forename: Suguru
authors.initials: S
authors.lastname: Oho
authors.forename: Masaki
authors.initials: M
authors.lastname: Sasai
mesh_terms: D000818:Animals; D019521:Body Patterning; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D030562:Databases, Protein; D004330:Drosophila / Q000196:embryology* / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008938:Mitosis; D008954:Models, Biological; D008957:Models, Genetic; D015233:Models, Statistical; D015203:Reproducibility of Results; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C056478:bcd protein, Drosophila; C061245:hb protein, Drosophila