Analysis of slmo, a gene required for normal motor function in Drosophila melanogaster
The stereotyped motor behaviour of the Drosophila larva provides a useful model for the development and function of neural circuitry. However, the cellular and molecular basis of this behaviour is poorly understood. Reported in this thesis is an analysis of slowmo (slmo), a gene previously shown to be expressed in the developing embryonic central nervous system of Drosophila. Null mutants of slmo are able to hatch, but the resulting larvae exhibit a progressive phenotype of defective locomotor activity. An enhancer trap, P(GAL4)c682, which is inserted in the slmo locus, reports expression in a subset of neurons within the embryonic, larval and adult central nervous systems. Inactivation of marked neurons with tetanus toxin light chain leads to severely impaired motor function, but not total paralysis. Affected embryos are capable of some sporadic movements, but are unable to hatch and normal peristaltic contraction waves are largely absent. The slmo gene is shown to encode a member of a novel family of conserved proteins of unknown function. GFP fusions of Slmo are shown to localise to the mitochondria in a cultured cell line. Two novel slmo related genes, termed pre/i/ (pre!) and real-time (retm), are identified in Drosophila. The prel gene is expressed ubiquitously during embryonic development, and disruption of the gene by a P-insertion results in lethality during larval development. retm encodes a member of a novel subclass of larger Slmo related proteins which contain the conserved CRAL- TRIO domain thought to be involved in the transport of small hydrophobic ligands. GFP fusions of both Prel and Retm are also associated with the mitochondria in cell culture, suggesting this might be true all proteins of this family. Using a yeast-2-hybrid approach, the identification of candidate Slmo interacting proteins is described, providing a basis for future work on the function of Slmo.