Regulation of Cubitus interruptus and the Ci signaling complex by Hedgehog signaling.

摘要

The Hedgehog (Hh) signaling pathway plays a vital role in many developmental pathways. Much of our understanding of this pathway comes from studies using Drosophila. The pathway gets its name from the Hh morphogen that regulates differential gene expression through the zinc finger transcription factor Cubitus interruptus (Ci).;In the imaginal discs of Drosophila, the secreted Hh is expressed in posterior compartment cells and crosses the anterior/posterior (A/P) compartment boundary where it encounters Hh responsive anterior cells. In anterior cells that receive modest levels of Hh, Ci is stabilized in its full-length form, Ci-155, and is able to shuttle into the nucleus. Away from the A/P boundary some of Ci-155 is tethered in the cytoplasm but most of Ci-155 is cleaved into a smaller form (Ci-75) that then goes into the nucleus to repress some Hh target genes, including dpp and hh. A number of molecules have been discovered that play a role in different aspects of Ci regulation.;In this dissertation, several different aspects of Hh signaling were investigated. Using several different mutations, the Ci signaling complex was genetically dissected to analyze the roles of the complex components in Ci regulation. This data suggested that each component had distinct roles in Ci regulation, but the complex still acted cooperatively in regulating Ci.;Genetic studies were also done to analyze how Hh signaling is modified over time and in different locations. In the wing disc the range of Hh signaling is modulated over time due to a negative feedback loop that decreases the amount of the Hh receptor Ptc, so that Hh can travel further into the anterior compartment. Other genetic experiments were done indicating that Hh signaling is modified in different regions of the wing disc.