Dynamical analysis of regulatory interactions in the gap gene system of Drosophila melanogaster

Genetic studies have revealed that segment determination in Drosophila melanogaster is based on hierarchical regulatory interactions among maternal coordinate and zygotic segmentation genes. The gap gene system constitutes the most upstream zygotic layer of this regulatory hierarchy, responsible for the initial interpretation of positional information encoded by maternal gradients. We present a detailed analysis of regulatory interactions involved in gap gene regulation based on gap gene circuits, which are mathematical gene network models used to infer regulatory interactions from quantitative gene expression data. Our models reproduce gap gene expression at high accuracy and temporal resolution. Regulatory interactions found in gap gene circuits provide consistent and sufficient mechanisms for gap gene expression, which largely agree with mechanisms previously inferred from qualitative studies of mutant gene expression patterns. Our models predict activation of Kr by Cad and clarify several other regulatory interactions. Our analysis suggests a central role for repressive feedback loops between complementary gap genes. We observe that repressive interactions among overlapping gap genes show anteroposterior asymmetry with posterior dominance. Finally, our models suggest a correlation between timing of gap domain boundary formation and regulatory contributions from the terminal maternal system.     

Analysis of maternal effect mutant combinations elucidates regulation and function of the overlap of hunchback and Krüppel gene expression in the Drosophila blastoderm embryo

The metameric organisation of the Drosophila embryo is generated early during development, due to the action of maternal effect and zygotic segmentation and homeotic genes. The gap genes participate in the complex process of pattern formation by providing a link between the maternal and the zygotic gene activities. Under the influence of maternal gene products they become expressed in distinct domains along the anteroposterior axis of the embryo; negative interactions between neighboring gap genes are thought to be involved in establishing the expression domains. The gap gene activities in turn are required for the correct patterning of the pair-rule genes; little is known, however, about the underlying mechanisms. We have monitored the distribution of gap and pair-rule genes in wild-type embryos and in embryos in which the anteroposterior body pattern is greatly simplified due to combinations of maternal effect mutations (staufen exuperantia, vasa exuperantia, vasa exuperantia, bicoid oskar, bicoid oskar torsolike, vasa torso exuperantia). We show that the domains of protein distribution of the gap genes hunchback and Krüppel overlap in wild-type embryos. Based on the analysis of the maternal mutant combinations, we suggest an explanation of how this overlap is generated. Furthermore, our data show that different constellations of gap gene activities provide different input for the pair-rule genes, and thus strongly suggest that the overlap of hunchback and Krüppel in wild-type is functional in the formation of the patterns of pair-rule genes.     

Control of the initiation of homeotic gene expression by the gap genes giant and tailless in Drosophila

The process of segmentation in Drosophila is controlled by both maternal and zygotic genes. Members of the gap class of segmentation genes play a key role in this process by interpreting maternal information and controlling the expression of pair-rule and homeotic genes. We have analyzed the pattern of expression of a variety of homeotic, pair-rule, and gap genes in tailless and giant gap mutants. tailless acts in two domains, one anterodorsal and one posterior. In its anterior domain tailless exerts a repressive effect on the expression of fushi tarazu, hunchback, and Deformed. In its posterior domain of action, tailless is responsible for the establishment of Abdominal-B expression and demarcating the posterior boundary of the initial domain of expression of Ultrabithorax. giant is an early zygotic regulator of the gap gene hunchback: in giant- embryos, alterations in the anterior domain of hunchback expression are visible by the beginning of cycle 14. giant also regulates the establishment of the expression patterns of Antennapedia and Abdominal-B. In particular, giant is the factor that controls the anterior limit of early Antennapedia expression.     

Interactions of the Drosophila gap gene giant with maternal and zygotic pattern-forming genes.

The Drosophila gene giant (gt) is a segmentation gene that affects anterior head structures and abdominal segments A5-A7. Immunolocalization of the gt product shows that it is a nuclear protein whose expression is initially activated in an anterior and a posterior domain. Activation of the anterior domain is dependent on the maternal bicoid gradient while activation of the posterior domain requires maternal nanos gene product. Initial expression is not abolished by mutations in any of the zygotic gap genes. By cellular blastoderm, the initial pattern of expression has evolved into one posterior and three anterior stripes of expression. The evolution, position and width of these stripes are dependent on interactions between gt and the other gap genes. In turn, gt activity in these domains affects the expression of the other gap genes. These interactions, typical of the cross-regulation previously observed among gap genes, confirm that gt is a member of the gap gene class whose function is necessary to establish the overall pattern of gap gene expression. After cellular blastoderm, gt protein continues to be expressed in the head region in parts of the maxillary and mandibular segments as well as in the labrum. Expression is never detected in the labial or thoracic segment primordia but persists in certain head structures, including the ring gland, until the end of embryonic development.