Mid-Embryo Patterning and Precision in <i>Drosophila</i> Segmentation: Krüppel Dual Regulation of <i>hunchback</i>

<div><p>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 <i>Drosophila</i> (fruit fly) embryos. The gap gene <i>hunchback</i> (<i>hb</i>) 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 <i>hb</i> expression can have significant effects in the development of the body plan. To investigate the factors contributing to <i>hb</i> precision, we used fine spatial and temporal resolution data to develop a quantitative model for the regulation of <i>hb</i> expression in the mid-embryo. In particular, modelling <i>hb</i> 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 <i>Krüppel</i> (<i>Kr</i>) 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 <i>hb</i> and high Kr concentration repressing <i>hb</i>. The processes of gene expression (transcription, translation, transport) are intrinsically random. We used stochastic simulations to characterize the noise generated in <i>hb</i> 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 <i>Kr-</i> mutant embryos. Further, Kr regulation can decrease uncertainty in mid-embryo <i>hb</i> 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.</p>