An extracellular biochemical screen reveals that FLRTs and Unc5s mediate neuronal subtype recognition in the retina.
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.
['Visser|Jasper J|JJ|', 'Cheng|Yolanda|Y|', 'Perry|Steven C|SC|', 'Chastain|Andrew Benjamin|AB|', 'Parsa|Bayan|B|', 'Masri|Shatha S|SS|', 'Ray|Thomas A|TA|', 'Kay|Jeremy N|JN|', 'Wojtowicz|Woj M|WM|']
D000818:Animals D001671:Biochemistry D002450:Cell Communication D020869:Gene Expression Profiling D008562:Membrane Glycoproteins D051379:Mice D046228:Microarray Analysis D000075386:Netrin Receptors D009474:Neurons D011485:Protein Binding D025941:Protein Interaction Mapping D020543:Proteome D011956:Receptors, Cell Surface D012160:Retina
retina inner plexiform layer mouse starburst amacrine cells axon guidance biochemistry laminar organization neuroscience receptor-ligand interactions