Search

Patterning of body parts in multicellular organisms relies on the interpretation of transcription factor (TF) concentrations by genetic networks. To determine the extent by which absolute TF concentration dictates gene expression and morphogenesis programs that ultimately lead to patterns in Drosophila embryos, we manipulate maternally supplied patterning determinants and measure readout concentration at the position of various developmental markers. When we increase the overall amount of the maternal TF Bicoid (Bcd) fivefold, Bcd concentrations in cells at positions of the cephalic furrow, an early morphological marker, differ by a factor of 2. This finding apparently contradicts the traditional threshold-dependent readout model, which predicts that the Bcd concentrations at these positions should be identical. In contrast, Bcd concentration at target gene expression boundaries is nearly unchanged early in development but adjusts dynamically toward the same twofold change as development progresses. Thus, the Drosophila segmentation gene network responds faithfully to Bcd concentration during early development, in agreement with the threshold model, but subsequently partially adapts in response to altered Bcd dosage, driving segmentation patterns toward their WT positions. This dynamic response requires other maternal regulators, such as Torso and Nanos, suggesting that integration of maternal input information is not achieved through molecular interactions at the time of readout but through the subsequent collective interplay of the network. [ABSTRACT FROM AUTHOR]

In Drosophila melanogaster, cis-regulatory modules that are activated by the Notch cell--cell signaling pathway all contain two types of transcription factor binding sites: those for the pathway's transducing factor Suppressor of Hairless [Su(H)] and those for one or more tissue- or cell type--specific factors called ''local activators.'' The use of different ''Su(H) plus local activator'' motif combinations, or codes, is critical to ensure that only the correct subset of the broadly utilized Notch pathway's target genes are activated in each developmental context. However, much less is known about the role of enhancer ''architecture''--the number, order, spacing, and orientation of its component transcription factor binding motifs--in determining the module's specificity. Here we investigate the relationship between architecture and function for two Notch-regulated enhancers with spatially distinct activities, each of which includes five high-affinity Su(H) sites. We find that the first, which is active specifically in the socket cells of external sensory organs, is largely resistant to perturbations of its architecture. By contrast, the second enhancer, active in the ''non-SOP'' cells of the proneural clusters from which neural precursors arise, is sensitive to even simple rearrangements of its transcription factor binding sites, responding with both loss of normal specificity and striking ectopic activity. Thus, diverse cryptic specificities can be inherent in an enhancer's particular combination of transcription factor binding motifs. We propose that for certain types of enhancer, architecture plays an essential role in determining specificity, not only by permitting factor--factor synergies necessary to generate the desired activity, but also by preventing other activator synergies that would otherwise lead to unwanted specificities. [ABSTRACT FROM AUTHOR]