High bicoid levels render the terminal system dispensable for Drosophila head development

In Drosophila, the gradient of the Bicoid (Bcd) morphogen organizes the anteroposterior axis while the ends of the embryo are patterned by the maternal terminal system. At the posterior pole, expression of terminal gap genes is mediated by the local activation of the Torso receptor tyrosine kinase (Tor). At the anterior, terminal gap genes are also activated by the Tor pathway but Bcd contributes to their activation. Here we present evidence that Tor and Bcd act independently on common target genes in an additive manner. Furthermore, we show that the terminal maternal system is not required for proper head development, since high levels of Bcd activity can functionally rescue the lack of terminal system activity at the anterior pole. This observation is consistent with a recent evolution of an anterior morphogenetic center consisting of Bcd and anterior Tor function.     

Bicoid - morphogen function revisited

Bicoid (Bcd) functions as a morphogen during Drosophila development. Accordingly, bcd mRNA is maternally localized to the anterior pole of the embryo, and Bcd forms an anterior/posterior gradient, which functions in a concentration dependent fashion. Thus, nuclei receiving identical amounts of Bcd should express the same target genes. However, we found that ectopic, uniform expression of Bcd causes anterior gene expression in the posterior with mirror image polarity, indicating that one or several additional factors must provide positional information. Recently, we have shown that one of these factors is Capicua (Cic), a ubiquitous maternal repressor that is down-regulated at the embryonic termini by maternal Torso, a key component of the maternal terminal system. Cic acts on Bcd dependent enhancer elements by repression and thereby controls the posterior limit of Bcd target gene expression. Based on these new findings, we propose that spatial control of gene expression in the anterior region of the embryo is not solely the result of Bcd morphogen action. Rather, it relies on a "morphogenic network" that integrates the terminal system and Bcd activities, providing both polarity and spatial information to the prospective head region of the developing embryo.     

Enhancer sequences influence the role of the amino-terminal domain of bicoid in transcription

Bicoid (Bcd) is a Drosophila melanogaster morphogenetic gradient that controls embryonic patterning by activating target gene expression in a concentration-dependent manner. In this study we describe experiments to determine how different enhancers respond to Bcd distinctively, focusing on two natural Bcd-responsive enhancer elements, hunchback (hb) and knirps (kni). Our results show that, on the hb enhancer element, the amino-terminal domain of Bcd (residues 1 to 91) plays primarily an inhibitory role, whereas on the kni enhancer element this same Bcd domain plays a positive role at low protein concentrations. We further demonstrate that while the amino-terminal domain is largely dispensable for cooperative binding to the hb enhancer element, it is preferentially required for cooperative binding to the kni enhancer element. Alteration of the arrangement of Bcd binding sites in the kni enhancer element reduces the role of the amino-terminal domain in cooperative DNA binding but increases the effectiveness of the self-inhibitory function. In addition, elimination of symmetric pairs of Bcd binding sites in the kni enhancer element reduces both DNA binding and activation by Bcd. We propose that the amino-terminal domain of Bcd is an enhancer-specific switch that contributes to the protein's ability to activate different target genes in distinct manners.     

The molecular chaperone Hsp90 is required for mRNA localization in Drosophila melanogaster embryos

Localization of maternal nanos mRNA to the posterior pole is essential for development of both the abdominal segments and primordial germ cells in the Drosophila embryo. Unlike maternal mRNAs such as bicoid and oskar that are localized by directed transport along microtubules, nanos is thought to be trapped as it swirls past the posterior pole during cytoplasmic streaming. Anchoring of nanos depends on integrity of the actin cytoskeleton and the pole plasm; other factors involved specifically in its localization have not been described to date. Here we use genetic approaches to show that the Hsp90 chaperone (encoded by Hsp83 in Drosophila) is a localization factor for two mRNAs, nanos and pgc. Other components of the pole plasm are localized normally when Hsp90 function is partially compromised, suggesting a specific role for the chaperone in localization of nanos and pgc mRNAs. Although the mechanism by which Hsp90 acts is unclear, we find that levels of the LKB1 kinase are reduced in Hsp83 mutant egg chambers and that localization of pgc (but not nos) is rescued upon overexpression of LKB1 in such mutants. These observations suggest that LKB1 is a primary Hsp90 target for pgc localization and that other Hsp90 partners mediate localization of nos.