FlpStop, a tool for conditional gene control in Drosophila

Abstract

Manipulating gene function cell type-specifically is a common experimental goal in <i>Drosophila</i> 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 <i>apterous</i>, a regulator of wing development. Next, we produced conditional null alleles of <i>Glutamic acid decarboxylase 1</i> (<i>Gad1</i>) and <i>Resistant to dieldrin</i> (<i>Rdl</i>), genes vital for GABAergic neurotransmission, as well as <i>cacophony</i> (<i>cac</i>) and <i>paralytic</i> (<i>para</i>), voltage-gated ion channels central to neuronal excitability. To demonstrate the utility of this approach, we manipulated <i>cac</i> 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.