title: Caenorhabditis elegans flamingo cadherin fmi-1 regulates GABAergic neuronal development.
abstract: In a genetic screen for regulators of synaptic morphology, we identified the single Caenorhabditis elegans flamingo-like cadherin fmi-1. The fmi-1 mutants exhibit defective axon pathfinding, reduced synapse number, aberrant synapse size and morphology, as well as an abnormal accumulation of synaptic vesicles at nonsynaptic regions. Although FMI-1 is primarily expressed in the nervous system, it is not expressed in the ventral D-type (VD) GABAergic motorneurons, which are defective in fmi-1 mutants. The axon and synaptic defects of VD neurons could be rescued when fmi-1 was expressed exclusively in non-VD neighboring neurons, suggesting a cell nonautonomous action of FMI-1. FMI-1 protein that lacked its intracellular domain still retained its ability to rescue the vesicle accumulation defects of GABAergic motorneurons, indicating that the extracellular domain was sufficient for this function of FMI-1 in GABAergic neuromuscular junction development. Mutations in cdh-4, a Fat-like cadherin, cause similar defects in GABAergic motorneurons. The cdh-4 is expressed by the VD neurons and seems to function in the same genetic pathway as fmi-1 to regulate GABAergic neuron development. Thus, fmi-1 and cdh-4 cadherins might act together to regulate synapse development and axon pathfinding.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Elvis Huarcaya
authors.initials: EH
authors.lastname: Najarro
authors.forename: Lianna
authors.initials: L
authors.lastname: Wong
authors.forename: Mei
authors.initials: M
authors.lastname: Zhen
authors.forename: Edgar Pinedo
authors.initials: EP
authors.lastname: Carpio
authors.forename: Alexandr
authors.initials: A
authors.lastname: Goncharov
authors.forename: Gian
authors.initials: G
authors.lastname: Garriga
authors.forename: Erik A
authors.initials: EA
authors.lastname: Lundquist
authors.forename: Yishi
authors.initials: Y
authors.lastname: Jin
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ackley
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology* / Q000254:growth & development*; D059330:GABAergic Neurons / Q000502:physiology* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D016253:Microscopy, Immunoelectron; D009154:Mutation / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D013569:Synapses / Q000235:genetics; D013572:Synaptic Vesicles / Q000235:genetics
chemical_list: D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; C553209:FMI-1 protein, C elegans; C083970:R-cadherin; D049452:Green Fluorescent Proteins