title: Guidance-cue control of horizontal cell morphology, lamination, and synapse formation in the mammalian outer retina.
abstract: In the vertebrate retina, neuronal circuitry required for visual perception is organized within specific laminae. Photoreceptors convey external visual information to bipolar and horizontal cells at triad ribbon synapses established within the outer plexiform layer (OPL), initiating retinal visual processing. However, the molecular mechanisms that organize these three classes of neuronal processes within the OPL, thereby ensuring appropriate ribbon synapse formation, remain largely unknown. Here we show that mice with null mutations in Sema6A or PlexinA4 (PlexA4) exhibit a pronounced defect in OPL stratification of horizontal cell axons without any apparent deficits in bipolar cell dendrite or photoreceptor axon targeting. Furthermore, these mutant horizontal cells exhibit aberrant dendritic arborization and reduced dendritic self-avoidance within the OPL. Ultrastructural analysis shows that the horizontal cell contribution to rod ribbon synapse formation in PlexA4⁻/⁻ retinas is disrupted. These findings define molecular components required for outer retina lamination and ribbon synapse formation.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Ryota L
authors.initials: RL
authors.lastname: Matsuoka
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jiang
authors.forename: Ivy S
authors.initials: IS
authors.lastname: Samuels
authors.forename: Kim T
authors.initials: KT
authors.lastname: Nguyen-Ba-Charvet
authors.forename: Lu O
authors.initials: LO
authors.lastname: Sun
authors.forename: Neal S
authors.initials: NS
authors.lastname: Peachey
authors.forename: Alain
authors.initials: A
authors.lastname: Chédotal
authors.forename: King-Wai
authors.initials: KW
authors.lastname: Yau
authors.forename: Alex L
authors.initials: AL
authors.lastname: Kolodkin
mesh_terms: D000818:Animals; D003712:Dendrites / Q000648:ultrastructure; D005260:Female; D008297:Male; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins; D055495:Neurogenesis / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000648:ultrastructure; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000648:ultrastructure; D051248:Retinal Horizontal Cells / Q000166:cytology* / Q000648:ultrastructure*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology* / Q000648:ultrastructure; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D009419:Nerve Tissue Proteins; C492110:Plxna4 protein, mouse; D011956:Receptors, Cell Surface; C504203:Sema6a protein, mouse; D039961:Semaphorins