Hemidriver Drosophila Lines ("Split-halves")
About the GAL4 Split-half Fly Lines
The ability to reproducibly target expression of transgenes to small, defined subsets of cells is a key experimental tool for understanding many biological processes. The Drosophila nervous system has thousands of distinct cell types and it has generally not been possible to limit expression to one or a few cell types with standard fly lines. Intersectional methods can be used to achieve the desired specificity by allowing expression of the transgene only where two different enhancers overlap in their expression patterns.
Janelia researchers in the Rubin lab and the FlyLight project team greatly expanded the ability of researchers to use these intersectional methods to perform custom Drosophila circuit analysis in a recently published study. They created ~7,500 "hemidriver" Drosophila fly lines that allow the generation of cell-type specific split-GAL4 driver lines. These fly stocks are freely available through the Bloomington Stockcenter through an NIH grant, in a large coordinated effort from Janelia Drosophila Resources.
The Janelia researchers used the split-GAL4 intersectional method described in Luan et al. (2006) with optimized vectors described in Pfeiffer et al. (2010). The result is fly lines with individual enhancers to drive the expression of either GAL4’s DNA-binding domain (DBD) or an activation domain (AD) joined to a leucine-zipper dimerization domain. When expressed individually, each half is insufficient to activate transcription of an upstream activating sequence (UAS) reporter. When both AD and DBD are present in the same cell, they combine to make a functional transcription factor that can bind to tandem arrays of GAL4’s cognate UAS DNA sequence and activate transcription. Resultant transgenic “hemidriver” lines expressing either the p65 AD or GAL4 DBD domain under the control of an enhancer from the collection described in Jenett et al. (2012) were created. Using the combined hemidriver collections described in this study and Tirian et al. (2017), it may be possible to obtain useful split-GAL4 lines for more than three quarters of the cell types in the adult fly brain.
Hemidriver Drosophila lines are available from Bloomington.