Article

Morphogen gradient formation and action Insights from studying Bicoid protein degradation

Division of Biomedical Informatics, Cincinnati Children's Research Foundation, Cincinnati, OH, USA.
Fly (Impact Factor: 1.48). 07/2011; 5(3):242-6. DOI: 10.4161/fly.5.3.15837
Source: PubMed

ABSTRACT In a recent publication, we identified a novel F-box protein, encoded by fates-shifted (fsd), that plays a role in targeting Bcd for ubiquitination and degradation. Our analysis of mutant Drosophila embryos suggests that Bcd protein degradation is important for proper gradient formation and developmental fate specification. Here we describe further experiments that lead to an estimate of Bcd half-life, < 15 min, in embryos during the time of gradient formation. We use our findings to evaluate different models of Bcd gradient formation. With this new estimate, we simulate the Bcd gradient formation process in our own biologically realistic 2-D model. Finally, we discuss the role of Bcd-encoded positional information in controlling the positioning and precision of developmental decisions.

Download full-text

Full-text

Available from: Jun Ma, Jul 07, 2014
0 Followers
 · 
164 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: An important feature of development is the formation of patterns that are proportional to the overall size of the embryo. But how such proportionality, or scaling, is achieved mechanistically remains poorly understood. Furthermore, it is currently unclear whether organisms utilize similar or distinct mechanisms to achieve scaling within a species and between species. Here we investigate within-species scaling mechanisms for anterior-posterior (A-P) patterning in Drosophila melanogaster, focusing specifically on the properties of the Bicoid (Bcd) morphogen gradient. Using embryos from lines artificially selected for large and small egg volume, we show that large embryos have higher nuclear Bcd concentrations in the anterior than small embryos. This anterior difference leads to scaling properties of the Bcd gradient profiles: in broad regions of the large and small embryos along the A-P axis, normalizing their positions to embryo length reduces the differences in both the nuclear Bcd concentrations and Bcd-encoded positional information. We further trace the origin of Bcd gradient scaling by showing directly that large embryos have more maternally deposited bcd mRNA than small embryos. Our results suggest a simple model for how within-species Bcd gradient scaling can be achieved. In this model, the Bcd production rate, which is dependent on the total number of bcd mRNA molecules in the anterior, is scaled with embryo volume.
    Development 07/2011; 138(13):2741-9. DOI:10.1242/dev.064402 · 6.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Transcriptional activators are required to turn on the expression of genes in a eukaryotic cell. Activators bound to the enhancer can facilitate either the recruitment of RNA polymerase II to the promoter or its elongation. This article examines a few selected issues in understanding activator functions and activation mechanisms.
    Protein & Cell 11/2011; 2(11):879-88. DOI:10.1007/s13238-011-1101-7 · 2.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We describe a statistical model to dissect the noise in transcriptional bursts in a developmental system. We assume that, at any given moment of time, each copy of a native gene inside a cell can exist in either a bursting (active) or non-bursting (inactive) state. The experimentally measured total noise in the transcriptional states of a gene in a population of cells can be mathematically dissected into two contributing components: internal and external. While internal noise quantifies the stochastic nature of transcriptional bursts, external noise is caused by cell-to-cell differences including fluctuations in activator concentration. We use our developed methods to analyze the Drosophila Bicoid (Bcd) morphogen gradient system. For its target gene hunchback (hb), the noise properties can be recapitulated by a simplified gene regulatory model in which Bcd acts as the only input, suggesting that the external noise in hb transcription is primarily derived from fluctuations in the Bcd activator input. However, such a simplified gene regulatory model is insufficient to predict the noise properties of another Bcd target gene, orthodenticle (otd), suggesting that otd transcription is sensitive to additional external fluctuations beyond those in Bcd. Our results show that analysis of the relationship between input and output noise can reveal important insights into how a morphogen gradient system works. Our study also advances the knowledge about transcription at a fundamental level. jun.ma@cchmc.org Supplementary data are available at Bioinformatics online.
    Bioinformatics 02/2012; 28(7):970-5. DOI:10.1093/bioinformatics/bts068 · 4.62 Impact Factor