Abstract
The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network.
Highlights
How genes contribute to pattern formation is one of the central questions of modern developmental biology
There are two very different approaches to the study of pattern formation: Traditional developmental genetics investigates the role of particular factors in great mechanistic detail, while newly developed systems-biology methods study many factors in parallel but usually remain rather general in their conclusions
Our analysis closely follows that of tll in [10], and focuses on the last two cleavage cycles before gastrulation (C13 and C14A; cleavage cycles and time classes are defined in Methods) [23]
Summary
How genes contribute to pattern formation is one of the central questions of modern developmental biology. This question has been addressed using genetic and molecular approaches. Very powerful, these approaches have several important limitations: First, it is difficult to study expression features which are not affected by a particular mutation (see below). It is difficult to establish whether known regulatory interactions are necessary, and sufficient to account for patterning in the wild-type system [2]. We show how such an approach can be used to investigate the patterning function of a particular gene in its wild-type context in a rigorous and quantitative manner
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
