title: An extracellular biochemical screen reveals that FLRTs and Unc5s mediate neuronal subtype recognition in the retina.
abstract: In the inner plexiform layer (IPL) of the mouse retina, ~70 neuronal subtypes organize their neurites into an intricate laminar structure that underlies visual processing. To find recognition proteins involved in lamination, we utilized microarray data from 13 subtypes to identify differentially-expressed extracellular proteins and performed a high-throughput biochemical screen. We identified ~50 previously-unknown receptor-ligand pairs, including new interactions among members of the FLRT and Unc5 families. These proteins show laminar-restricted IPL localization and induce attraction and/or repulsion of retinal neurites in culture, placing them in an ideal position to mediate laminar targeting. Consistent with a repulsive role in arbor lamination, we observed complementary expression patterns for one interaction pair, FLRT2-Unc5C, in vivo. Starburst amacrine cells and their synaptic partners, ON-OFF direction-selective ganglion cells, express FLRT2 and are repelled by Unc5C. These data suggest a single molecular mechanism may have been co-opted by synaptic partners to ensure joint laminar restriction.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Visser
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Perry
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Andrew Benjamin
authors.initials: AB
authors.lastname: Chastain
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Bayan
authors.initials: B
authors.lastname: Parsa
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Shatha S
authors.initials: SS
authors.lastname: Masri
authors.affiliation: Department of Neurobiology, Duke University School of Medicine, Durham, United States.|Department of Opthalmology, Duke University School of Medicine, Durham, United States.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Ray
authors.affiliation: Department of Neurobiology, Duke University School of Medicine, Durham, United States.|Department of Opthalmology, Duke University School of Medicine, Durham, United States.
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Kay
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Woj M
authors.initials: WM
authors.lastname: Wojtowicz
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods; D002450:Cell Communication; D020869:Gene Expression Profiling; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D046228:Microarray Analysis; D000075386:Netrin Receptors; D009474:Neurons / Q000502:physiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020543:Proteome / Q000032:analysis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012160:Retina / Q000033:anatomy & histology* / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; D000075386:Netrin Receptors; D020543:Proteome; D011956:Receptors, Cell Surface
keywords: axon guidance; biochemistry; inner plexiform layer; laminar organization; mouse; neuroscience; receptor-ligand interactions; retina; starburst amacrine cells