Growth of an animal from an egg to an adult requires the generation of thousands of different kinds of cells. Each cell must respond correctly to the molecular signals that specify its ultimate fate, for the consequences of mistakes are death or disease. The question of how cells discriminate between signals that differ only subtly from one another is particularly challenging. A textbook example is sex determination in the fruit fly, Drosophila, yet, as shown in this work, the textbook version is wrong in fundamental details. This project exploits unique genetic tools to determine how flies tell whether they have one X chromosome and develop as males or two Xs and grow as females. The expectation is that responses to signals occur in small steps and that the steps reinforce one another. The result is an amplification of a small initial difference into a reliable response. Females initiate development first because of the slightly higher two-X signal. This leads to a chain of events that simultaneously increases the female program while dampening the male one, thus ensuring proper female development. Reciprocally, the lower initial signal in males promotes male development by making it progressively harder to carry out the female program. Because the molecules involved are general regulators of animal development, the mechanisms by which they work in fly sex should apply to many aspects of animal development. The broader impact of this work rests on the principle of analogy. Experimental systems like the fly can reveal levels of detail that approaches what actually exists in the living organism. This lets researchers in less tractable systems take shortcuts to the correct answers. The textbook status of sex determination reinforces the educational and scientific impacts of the lessons and analogies, but also makes it imperative to correct the textbooks.
