Analysis of <i>Drosophila</i> photoreceptor axon guidance in eye-specific mosaics

TLDR

During Drosophila eye development, photoreceptor axons fasciculate into bundles that project to the optic lobes, where R1–R6 terminate in the lamina and R7–R8 extend through the lamina to distinct medulla layers, and the receptor tyrosine phosphatase PTP69D has been implicated in motor axon targeting and R1–R6 guidance. The study aimed to identify genes essential for photoreceptor axon guidance by creating genetic mosaics in which mutant photoreceptor axons develop within a largely wild‑type brain. Using this mosaic system, a large‑scale saturation mutagenesis uncovered new alleles of the PTP69D gene. PTP69D is required for correct R7 axon targeting; mutants mis‑target R7 to the R8 level, while R1–R6 occasionally overshoot the lamina, suggesting PTP69D acts permissively by reducing adhesion to the pioneer R8 axon.

Abstract

ABSTRACT During development of the adult Drosophila visual system, axons of the eight photoreceptors in each ommatidium fasciculate together and project as a single bundle towards the optic lobes of the brain. Within the brain, individual photoreceptor axons from each bundle then seek specific targets in distinct layers of the optic lobes. The axons of photoreceptors R1-R6 terminate in the lamina, while R7 and R8 axons pass through the lamina to terminate in separate layers of the medulla. To identify genes required for photoreceptor axon guidance, including those with essential functions during early development, we have devised a strategy for the simple and efficient generation of genetic mosaics in which mutant photoreceptor axons innervate a predominantly wild-type brain. In a large-scale saturation mutagenesis performed using this system, we recovered new alleles of the gene encoding the receptor tyrosine phosphatase PTP69D. PTP69D has previously been shown to function in the correct targeting of motor axons in the embryo and R1-R6 axons in the visual system. Here, we show that PTP69D is also required for correct targeting of R7 axons. Whereas mutant R1-R6 axons occasionally extend beyond their normal targets in the lamina, mutant R7 axons often fail to reach their targets in the medulla, stopping instead at the same level as the R8 axon. These targeting errors are difficult to reconcile with models in which PTP69D plays an instructive role in photoreceptor axon targeting, as previously proposed. Rather, we suggest that PTP69D plays a permissive role, perhaps reducing the adhesion of R1-R6 and R7 growth cones to the pioneer R8 axon so that they can respond independently to their specific targeting cues.