Abstract
In early development, genes are expressed in spatial patterns which later define cellular identities and tissue locations. The mechanisms of such pattern formation have been studied extensively in early Drosophila (fruit fly) embryos. The gap gene hunchback (hb) is one of the earliest genes to be expressed in anterior-posterior (AP) body segmentation. As a transcriptional regulator for a number of downstream genes, the spatial precision of hb expression can have significant effects in the development of the body plan. To investigate the factors contributing to hb precision, we used fine spatial and temporal resolution data to develop a quantitative model for the regulation of hb expression in the mid-embryo. In particular, modelling hb pattern refinement in mid nuclear cleavage cycle 14 (NC14) reveals some of the regulatory contributions of simultaneously-expressed gap genes. Matching the model to recent data from wild-type (WT) embryos and mutants of the gap gene Krüppel (Kr) indicates that a mid-embryo Hb concentration peak important in thoracic development (at parasegment 4, PS4) is regulated in a dual manner by Kr, with low Kr concentration activating hb and high Kr concentration repressing hb. The processes of gene expression (transcription, translation, transport) are intrinsically random. We used stochastic simulations to characterize the noise generated in hb expression. We find that Kr regulation can limit the positional variability of the Hb mid-embryo border. This has been recently corroborated in experimental comparisons of WT and Kr- mutant embryos. Further, Kr regulation can decrease uncertainty in mid-embryo hb expression (i.e. contribute to a smooth Hb boundary) and decrease between-copy transcriptional variability within nuclei. Since many tissue boundaries are first established by interactions between neighbouring gene expression domains, these properties of Hb-Kr dynamics to diminish the effects of intrinsic expression noise may represent a general mechanism contributing to robustness in early development.
Highlights
In the early stages of Drosophila melanogaster segmentation, hunchback and other gap genes form broad expression domains along the anterior-posterior (AP) axis of the embryo
The model was developed and parameters were selected by matching deterministic model solutions to positions and relative intensities in mid-nuclear cleavage cycle 14 (NC14)
We have developed and tested a quantitative model of mutual interaction between Hb and Kr for regulation of hb gene expression at the mid-embryo
Summary
In the early stages of Drosophila melanogaster segmentation, hunchback (hb) and other gap genes form broad expression domains along the anterior-posterior (AP) axis of the embryo Their transcription is regulated by maternally-derived proteins and by cross- and self-effects of the gap proteins themselves. Comparisons of Hb and Bcd positional variability in the mid-embryo indicate that mature NC14 hb pattern is not entirely specified by Bcd concentration [8,9,10]: rather than a one-to-one correspondence, Hb displays about half the variability of Bcd [11] This means that the spatial precision that hb (and other gap genes) provide to their targets, the pair-rule genes, is about twice the precision supplied to the gaps by the maternal gradients [12]. We used the relative experimental intensities to sequentially (starting from data for 1 BS) set the relative transcription rates in the model for each bound state (bx)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 call
