title: Regulation of synaptic connectivity: levels of Fasciclin II influence synaptic growth in the Drosophila CNS.
abstract: Much of our understanding of synaptogenesis comes from studies that deal with the development of the neuromuscular junction (NMJ). Although well studied, it is not clear how far the NMJ represents an adequate model for the formation of synapses within the CNS. Here we investigate the role of Fasciclin II (Fas II) in the development of synapses between identified motor neurons and cholinergic interneurons in the CNS of Drosophila. Fas II is a neural cell adhesion molecule homolog that is involved in both target selection and synaptic plasticity at the NMJ in Drosophila. In this study, we show that levels of Fas II are critical determinants of synapse formation and growth in the CNS. The initial establishment of synaptic contacts between these identified neurons is seemingly independent of Fas II. The subsequent proliferation of these synaptic connections that occurs postembryonically is, in contrast, significantly retarded by the absence of Fas II. Although the initial formation of synaptic connectivity between these neurons is seemingly independent of Fas II, we show that their formation is, nevertheless, significantly affected by manipulations that alter the relative balance of Fas II in the presynaptic and postsynaptic neurons. Increasing expression of Fas II in either the presynaptic or postsynaptic neurons, during embryogenesis, is sufficient to disrupt the normal level of synaptic connectivity that occurs between these neurons. This effect of Fas II is isoform specific and, moreover, phenocopies the disruption to synaptic connectivity observed previously after tetanus toxin light chain-dependent blockade of evoked synaptic vesicle release in these neurons.
authors.affiliation: Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom. rbaines@bio.warwick.ac.uk
authors.forename: Richard A
authors.initials: RA
authors.lastname: Baines
authors.forename: Laurent
authors.initials: L
authors.lastname: Seugnet
authors.forename: Annemarie
authors.initials: A
authors.lastname: Thompson
authors.forename: Paul M
authors.initials: PM
authors.lastname: Salvaterra
authors.forename: Michael
authors.initials: M
authors.lastname: Bate
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000378:metabolism; D004330:Drosophila; D004625:Embryo, Nonmammalian; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D007814:Larva; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010507:Periodicity; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013744:Tetanus Toxin / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D012333:RNA, Messenger; D013744:Tetanus Toxin; C051642:fasciclin II; D008666:Metalloendopeptidases; C093556:zinc-endopeptidase, tetanus neurotoxin