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 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 that a single molecular mechanism may have been co-opted by synaptic partners to ensure joint laminar restriction.
Animal experimentation: All animal procedures were approved by the University of California, Berkeley (Office of Laboratory Animal Care (OLAC) protocol #R308) and they conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, the Public Health Service Policy and the Society for Neuroscience Policy on the Use of Animals in Neuroscience Research.
- Constance Cepko, Harvard University, United States
© 2015, Visser et al.
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