Modeling of the signaling networks in patterning and growth control of the Drosophila wing disc

Abstract

A major challenge in understanding patterning and growth control is how the signaling pathways are balanced to produce normal pattern and growth and how they interact to respond to aberrant signals. In the dissertation, we aim to develop a mathematical model which incorporates the Hippo pathway locating at the center of different regulatory pathways in the wing disc of Drosophila so as to be able to understand existing experimental results, to make experimentally-testable predictions, and to provide a platform for integrating and testing new results and incorporating other signaling pathways. The model we developed addresses the limitation of previous models due to lack of mechanistic details, and predicts all the primary characteristic phenotypes associated with the pathway. Moreover, the model supports two hypotheses, one of which have been confirmed by experiments. As using a mathematical model to facilitate the development of biology is contingent on parameters, the other specific aim of our work is to propose a new way to improve parameter estimation from experimental data. We identify the source for poor estimation in Fluorescence recovery after photobleaching (FRAP), a widely-used technique for quantitative measurement of molecular dynamics, and propose three feasible ways to improve parameter estimation. In addition, we also introduce sensitivity analysis to improve model identification in FRAP.