Eric C. Lai: Overview
We have extensively utilized the fruitfly Drosophila melanogaster, based on its wealth of sophisticated genetic tools and depth of comparative genomic data. We focused on 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 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 PNS patterning and other settings are altered by manipulating Notch signaling, lineage transcription factors and microRNAs, we have uncovered new strategies regarding developmental patterning. Moreover, our mechanistic and genomic studies have yielded broadly conserved concepts regarding transcriptional gene regulation, small RNA discovery and biogenesis, and mRNA processing (e.g. tissue-specific alternative 3’UTR utilization [Fig. 2], circularization, and RNA methylation). We have subsequently extended many of these principles into mammalian systems, including into aspects of mouse development.