FlpStop, a tool for conditional gene control in Drosophila .

Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous , a regulator of wing development. Next, we produced conditional null alleles of Glutamic acid decarboxylase 1 ( Gad1 ) and Resistant to dieldrin ( Rdl ), genes vital for GABAergic neurotransmission, as well as cacophony ( cac ) and paralytic ( para ), voltage-gated ion channels central to neuronal excitability. To demonstrate the utility of this approach, we manipulated cac in a specific visual interneuron type and discovered differential regulation of calcium signals across subcellular compartments. Thus, FlpStop will facilitate investigations into the interactions between genes, circuits, and computation.