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The split-GAL4 system allows you to restrict expression from a UAS construct to cells where the two components of the split-GAL4 activator are expressed. As shown below, the GAL4 DNA-binding domain fused to the Zip- protein-pairing domain can be expressed in one pattern, a transcriptional activation domain fused to the Zip+ protein-pairing domain can be expressed in another pattern and the UAS reporter construct will be expressed in the intersection of the two patterns.

As also shown below, this system can be extended to reflect three expression patterns by including a construct expressing a protein that competes for Zip- binding. This "Killer Zipper" protein, consisting of the GAL4 DNA-binding domain fused to the Zip+ protein-pairing domain, can be expressed directly under control of cell-specific regulatory sequences or indirectly under LexAop control.

Killer Zipper illustration originating in Dolan et al. (2017). Facilitating Neuron-Specific Genetic Manipulations in Drosophila melanogaster Using a Split GAL4 Repressor. Genetics 206: 775-784

An example is shown below of Killer Zipper expression eliminating split-GAL4 activation of UAS-Venus expression in the nerve cord, but not the brain lobes.

Killer Zipper illustration originating in Dolan et al. (2017). Facilitating Neuron-Specific Genetic Manipulations in Drosophila melanogaster Using a Split GAL4 Repressor. Genetics 206: 775-784

This method was described in Dolan et al. (2017). Facilitating Neuron-Specific Genetic Manipulations in Drosophila melanogaster Using a Split GAL4 Repressor. Genetics 206: 775--784.

Stk # Genotype
76253 w[*]; P{y[+t7.7] w[+mC]=13XLexAop2-KZip+.3XHA}su(Hw)attP5/CyO; TM6B, Tb[1]/MKRS
76254 w[*]; P{y[+t7.7] w[+mC]=13XLexAop2-KZip+.3XHA}attP2
76617 w[*]; P{y[+t7.7] w[+mC]=13XLexAop2-KZip+.3XHA}attP40; TM6B, Tb[1]/MKRS