Cell type-specific transcriptional regulation of the Drosophila FMRFamide neuropeptide gene.

We have used lacZ reporter gene constructs to study the promoter/enhancer regions of the Drosophila FMRFamide neuropeptide gene in germ line transformants. FMRFamide is normally expressed in approximately 60 diverse neurons of the larval CNS that represent approximately 15 distinct cell types. An 8 kb FMRFamide DNA fragment (including 5 kb of 5' upstream sequence) was sufficient to direct a pattern of lacZ expression that mimicked nearly all spatial aspects of the normal pattern. This result indicates that the cell-specific regulation of FMRFamide expression is largely generated by transcriptional mechanisms. Reporter gene expression was lost from selected cell types when smaller fragments were tested, suggesting that multiple control regions are included in the FMRFamide promoter. One region (a 300 bp fragment from -476 to -162) acted as an enhancer for 1 of the approximately 15 FMRFamide-positive cell types, the OL2 neurons. These results suggest that, in the mature nervous system, the complex pattern of FMRFamide neuropeptide gene expression derives from the activity of discrete, cell type-specific enhancers that are independently regulated.