Mechanisms of odor receptor gene choice in Drosophila.

A remarkable problem in neurobiology is how olfactory receptor neurons (ORNs) select, from among a large odor receptor repertoire, which receptors to express. We use computational algorithms and mutational analysis to define positive and negative regulatory elements that are required for selection of odor receptor (Or) genes in the proper olfactory organ of Drosophila, and we identify an element that is essential for selection in one ORN class. Two odor receptors are coexpressed by virtue of the alternative splicing of a single gene, and we identify dicistronic mRNAs that each encode two receptors. Systematic analysis reveals no evidence for negative feedback regulation, but provides evidence that the choices made by neighboring ORNs of a sensillum are coordinated via the asymmetric segregation of regulatory factors from a common progenitor. We show that receptor gene choice in Drosophila also depends on a combinatorial code of transcription factors to generate the receptor-to-neuron map.