MOLECULAR AND GENETIC STUDIES OF CELLULAR REGULATORY MECHANISMS USING DROSOPHILA MELANOGASTER AS A MODEL SYSTEM

Open Access
Author:
Rohrbaugh, Margaret C.
Graduate Program:
Biochemistry, Microbiology, and Molecular Biology
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
June 05, 2003
Committee Members:
  • Zhi Chun Lai, Committee Chair
  • Ross Cameron Hardison, Committee Member
  • Richard W Ordway, Committee Member
  • Benjamin Franklin Pugh, Committee Member
  • Esther Siegfried, Committee Member
Keywords:
  • Drosophila
  • Yan
  • Cell Cycle
  • Notch Signaling
  • Development
  • Gp150
Abstract:
Proper organismal development and cell survival requires integration of a number of signaling pathways and regulatory molecules. Intracellular and extracellular molecules coordinate to regulate a number of cell functions including cell differentiation, proliferation and morphogenesis. Many of these molecules and signaling pathways are highly conserved throughout evolution. Due to this, studies in model organisms have been critical in defining the basic concepts that govern all cell functions. This thesis focuses on using Drosophila melanogaster as a model system. Drosophila has been an effective model system for nearly one hundred years helping to define the components necessary for processes such as neural and embryonic development. We demonstrate three effective uses of Drosophila. In the first study, we have identified an eye specific enhancer for the yan gene, a general inhibitor of differentiation. In the developing eye, yan is required to inhibit neuronal differentiation until proper inductive signaling is initiated. Analysis of the yan enhancer identified a regulatory mechanism involving the Notch pathway and Receptor Tyrosine Kinase (RTK) pathway mediated by the Drosophila EGF Receptor (DER). This model provides the first example where these two key pathways integrate in a competitive manner at the DNA sequence level. The second study identifies patterning and degeneration defects within the Drosophila ovary caused by mutations in gp150. In the eye, gp150 has been shown to be involved in regulating ommatidial assembly via interactions with components of the Notch pathway. Analysis of gp150’s expression pattern and mutant phenotype in the ovary indicate that it may be interacting with the Notch pathway in the ovary as well. The final study uses the eye as a model to study cell proliferation. We provide initial phenotypic characterization of a mutation in a novel tumor supressor gene. Combined, these three examples demonstrate the effectiveness of Drosophila as a model system. In particular, studies of the yan enhancer make a significant contribution to our understanding of the amount of integration required between major signaling pathways involved in cell development and differentiation.