bicoid (bcd) is a major patterning gene during early Drosophila development; it encodes a transcriptional activator that forms a morphogenetic gradient along the anterior-posterior (AP) axis of the embryo. The threshold model of Bcd function proposes that the cis-regulatory modules (CRMs) of Bcd target genes contain binding sites that make them differentially sensitive to Bcd concentration, and that sensitivity controls where they are expressed along the embryo length. However, several lines of evidence suggest that the simple threshold model for positioning target genes is incomplete. In this thesis the question of the specific role of Bcd in activating its target genes was asked. Several approaches were taken to address this question. A bioinformatic approach was used to identify novel Bcd-dependent CRMs and to characterize known and novel CRMs in terms of their clusters of Bcd binding sites. The aim of this analysis was to identify a correlation between Bcd cluster strength and CRM expression along AP axis. No significant correlations were found. To directly test the morphogen hypothesis, the Bcd gradient was manipulated to produce embryos with various levels of flat Bcd. These embryos were used to monitor gene expression genome-wide with the aim of identifying new targets and testing whether genes expressed in different positions are activated by different Bcd levels. A major prediction of the morphogen hypothesis is that target genes should show on or off expression responses in embryos with flat Bcd once their activation threshold is met. However, only a few target genes showed the predicted response. Also, the Bcd concentration required for activation of each tested target gene was much lower than that present in the wild-type Bcd gradient at the position of target gene activation. In conclusion it was found that the Bcd gradient does not pattern its target genes alone. Rather, these results are interpreted in the context of a combinatorial mode of regulation where Bcd is always acting with other patterning gradients, which include maternally expressed Hunchback (Hb) protein and the Torso-dependent terminal patterning system.
|Advisor:||Small, Stephen J.|
|Commitee:||Birnbaum, Kenneth, Desplan, Claude, Di Gregorio, Anna, Gunsalus, Kristin, Treisman, Jessica|
|School:||New York University|
|School Location:||United States -- New York|
|Source:||DAI-B 70/01, Dissertation Abstracts International|
|Subjects:||Biology, Molecular biology, Genetics|
|Keywords:||Bicoid, Drosophila, Embryo, Molecular genetics, Morphogen, Morphogen gradient|
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