Genetic analysis of the maintenance of neuronal morphology in Drosophila melanogaster

Abstract

Precise control of cellular morphology is critical for both the development and maintenance of nervous systems. In the developing Drosophila eye, normal photoreceptor cells establish and maintain a highly polarized architecture, with cell bodies and nuclei located apically in the epithelium, and axons extending basally into the brain. Disruption of the Dynactin complex, which activates the minus-end-directed microtubule motor protein Dynein, causes mislocalization of photoreceptor nuclei basally, even into the optic stalk and brain. Photoreceptors in animals mutant for the Dynactin subunit Glued retain apical markers, but have a bipolar-like morphology with the cell body translocated toward the brain and an apical process extending to the surface of the eye disc. Dynactin is required post-mitotically to maintain proper nuclear positioning. Using a genetic screen, I identified loss-of-function alleles of kinesin heavy chain, encoding a subunit of the plus-end-directed microtubule motor Kinesin, as suppressors of the rough eye and nuclear mispositioning in Glued mutants. Thus, a balance of minus-end-directed and plus-end-directed microtubule motor forces may be required to maintain nuclear position within postmitotic neurons.

(cont.) Establishment and maintenance of complex axonal trajectories is also a key feature of neuronal mophology. I identified a requirement for a novel cytoplasmic tyrosine phosphatase, PTPMEG, in these processes. Normal mushroom bodies, structures critical for insect learning and memory, have dorsally-projecting alpha lobe and medially-projecting beta lobe axons. Alpha lobes develop normally in ptpmeg mutants, but their pattern is not maintained. Instead, alpha lobe axons retract during pupation, resulting in thin and/or shortened alpha lobes. Meanwhile, beta lobe axons overextend at the midline. Removing ptpmeg function in mushroom bodies does not cause mutant phenotypes. ptpmeg mutants are rescued by pan-neuronal expression of wild-type Ptpmeg, but not by versions with disrupted phosphatase activity. These data suggest that Ptpmeg activity is required in another type of neuron to prevent mushroom body axon retraction. Ellipsoid body axons normally form a ring structure in the central brain. In ptpmeg mutants, the ellipsoid body axons develop abnormally, with the ventral side of the ring being discontinuous; the defect can be rescued by expression of wild-type Ptpmeg pan-neuronally.