An extracellular biochemical screen reveals that FLRTs and Unc5s mediate neuronal subtype recognition in the retina
Jasper J Visser,
Yolanda Cheng,
Steven C Perry,
Andrew Benjamin Chastain,
Bayan Parsa,
Shatha S Masri,
Thomas A Ray,
Jeremy N Kay,
Woj M Wojtowicz
Affiliations
Jasper J Visser
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Yolanda Cheng
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Steven C Perry
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Andrew Benjamin Chastain
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Bayan Parsa
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Shatha S Masri
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Thomas A Ray
Department of Neurobiology, Duke University School of Medicine, Durham, United States; Department of Opthalmology, Duke University School of Medicine, Durham, United States
Jeremy N Kay
Department of Neurobiology, Duke University School of Medicine, Durham, United States; Department of Opthalmology, Duke University School of Medicine, Durham, United States
Woj M Wojtowicz
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
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.
