IBN #9807892; Moses; Epidermal Growth Factor (EGF) was first discovered in vertebrates. It is a small protein that regulates the growth of many cells and their ability to stop dividing and form specialized cell types. EGF is secreted from cells that are sending an instructive signal and is received by other cells that then act on that signal. The target cells receive the EGF signal using a protein that penetrates thorough their surface called the EGF-receptor (EGFR) which can bind EGF. When EGFR has bound EGF on the outside of the target cell it becomes activated and begins to chemically modify other proteins on the inside of the cell (by adding phosphate to them). A chain reaction then follows with the sequential activation of a series of proteins on the inside of the cell, usually named for one of its links as the "ras signal transduction cascade". At the other end of this pathway are proteins that when activated can bind to DNA at specific sites and change the set of genes that the cell is using to make new proteins. Thus a signal from EGF acts through EGFR and the ras cascade in the target cell to alter its behavior.
This process is of great general significance in developmental biology. Many developmental processes are regulated by it. Over activation of the pathway can cause run-away cell division and is the most common cause of cancer in humans. However the normal functioning of the EGFR pathway is essential for the normal development of all animals, and their nervous systems in particular. Thus, the present proposal will study the role of EGFR signaling in the developing compound eye of the fruit fly, Drosophila melanogaster. This model organism has been chosen because decades of genetic research using this animal have made it possible to conduct more sophisticated genetic experiments than are possible in vertebrates. The insect compound eye contains many similar facets, but each has only eight photoreceptor cells. It is thus possible to approach a real understanding of the development of this relatively simple model nervous system. Temperature-sensitive mutation of the EGFR gene in flies were produced that permit Dr. Moses to grow live flies with functional EGFR, and to kill the activity of the receptor simply by raising the temperature at any time. In the proposed experiments the P.I. will undertake more detailed studies with the temperature sensitive mutations in order to understand how the EGF signal is controlled in flies. In addition, of two new genes recently discovered in the EGFR pathway will be cloned.
