Fig. 1 Mutant flies with fewer or more bristles than normal.
Control of developmental patterning in Drosophila by Notch signaling and microRNAs
As a laboratory of developmental biology, our guiding interest is to comprehend how complex biological patterns can be assembled with stereotyped precision. This requires a detailed understanding of how cells come to execute appropriate behaviors — be it adoption of specific cell fates, proliferation, or apoptosis — and do so at the right times, in the right places, and in the right numbers. Dysfunction of processes that direct normal tissue patterning results not only in developmental disorder but also underlies adult disease. Tellingly, many factors whose mutation is relevant to human cancer were first identified and characterized with respect to development in model organisms.
We choose the fruitfly Drosophila melanogaster as our principal model system, based on its wealth of sophisticated genetic tools and depth of comparative genomic data. We study two topics in developmental patterning: (1) determination of cell fates by a cell-cell signaling cascade known as the Notch pathway and (2) the biological activities of microRNAs, a newly defined class of endogenous small regulatory RNAs. We study these with respect to the development of several fly tissues that are intricately yet robustly patterned. For example, the body surface of the fly is covered with mechanosensory bristles, which constitute most of its peripheral nervous system (Figure 1). The pattern of bristles is very stable in wildtype flies but is readily amenable to genetic manipulation.
By studying how bristle patterning and other developmental events are altered by manipulating Notch signaling and microRNA function, we hope to better understand how these molecular systems organize pattern elements. Conversely, we can use these developmental paradigms in forward genetic screens to isolate novel genes that control developmental patterning.