| Little is known about how individual olfactory receptor neurons (ORNs) select, from among many odor receptor genes, which genes to express. The process is critical to the establishment of ORN populations that encode olfactory information. A combinatorial code of transcriptional activation and repression has been proposed to underlie receptor gene choice in the fruit fly Drosophila. However, the components of this code are largely unknown. Here we study Acj6 (Abnormal chemosensory jump 6), a POU-domain transcription factor essential for the specification of ORN identity and Or (odor receptor) gene expression in the maxillary palp, one of the two olfactory organs of the fly. We systematically examine the role of Acj6 in the maxillary palp and in a major subset of antenna) ORNs. We define an Acj6 binding site by a reiterative in vitro selection process, find that Or genes regulated by Acj6 contain this site, and show by mutational analysis that these sites are required in vivo for normal Or expression. We find that a novel ORN class in acj6 adults arises from ectopic expression of a larval Or gene.;We identify multiple acj6 transcripts, encoding different proteins, in the olfactory organs. We show that flies expressing a single splice form of acj6 have defects in ORN responses and Or gene expression. A single splice form can regulate Or gene expression both positively and negatively. Splice forms differ in their ability to specify neuronal identities and different ORN classes may require different splice form combinations.;We conclude that Acj6 acts directly in the process of receptor gene choice, that it plays a dual role, positive and negative, in the logic of the process, and that it acts in the partitioning of the larval and adult receptor repertoires. We have strong evidence that different Acj6 splice forms act in concert to fill this dual role. Thus the results support a model in which odor receptor gene choice is governed by a combinatorial code of transcription factors, in which dual regulation and alternative splicing provide two means of expanding and enriching the code. |
