title: Cellular mechanisms governing synaptic development in Drosophila melanogaster.
abstract: The neuromuscular connections of Drosophila are ideally suited for studying synaptic function and development. Hypotheses about cell recognition can be tested in a simple array of pre- and postsynaptic elements. Drosophila muscle fibers are multiply innervated by individually identifiable motoneurons. The neurons express several synaptic cotransmitters, including glutamate, proctolin, and octopamine, and are specialized by their synaptic morphology, neurotransmitters, and connectivity. During larval development the initial motoneuron endings grow extensively over the surface of the muscle fibers, and differentiate synaptic boutons of characteristic morphology. While considerable growth occurs postembryonically, the initial wiring of motoneurons to muscle fibers is accomplished during mid-to-late embryogenesis (stages 15-17). Efferent growth cones sample multiple muscle fibers with rapidly moving filopodia. Upon reaching their target muscle fibers, the growth cones rapidly differentiate into synaptic contacts whose morphology prefigures that of the larval junction. Mismatch experiments show that growth cones recognize specific muscle fibers, and can do so when the surrounding musculature is radically altered. However, when denied their normal targets, motoneurons can establish functional synapses on alternate muscle fibers. Blocking synaptic activity with either injected toxins or ion channel mutants does not derange synaptogenesis, but may influence the number of motor ending processes. The molecular mechanisms governing cellular recognition during synaptogenesis remain to be identified. However, several cell surface glycoproteins known to mediate cellular adhesion events in vitro are expressed by the developing synapses. Furthermore, enhancer detector lines have identified genes with expression restricted to small subsets of muscle fibers and/or motoneurons during the period of synaptogenesis. These observations suggest that in Drosophila a mechanism of target chemoaffinity may be involved in the genesis of stereotypic synaptic wiring.
authors.affiliation: Department of Biology, Yale University, New Haven, Connecticut 06511.
authors.forename: H
authors.initials: H
authors.lastname: Keshishian
authors.forename: A
authors.initials: A
authors.lastname: Chiba
authors.forename: T N
authors.initials: TN
authors.lastname: Chang
authors.forename: M S
authors.initials: MS
authors.lastname: Halfon
authors.forename: E W
authors.initials: EW
authors.lastname: Harkins
authors.forename: J
authors.initials: J
authors.lastname: Jarecki
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Anderson
authors.forename: S
authors.initials: S
authors.lastname: Cash
authors.forename: M E
authors.initials: ME
authors.lastname: Halpern
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000196:embryology / Q000254:growth & development*; D004742:Enhancer Elements, Genetic; D009024:Morphogenesis; D009046:Motor Neurons / Q000502:physiology; D009154:Mutation; D009411:Nerve Endings / Q000254:growth & development; D009469:Neuromuscular Junction / Q000196:embryology / Q000254:growth & development; D010641:Phenotype; D013569:Synapses / Q000502:physiology*