An extracellular biochemical screen reveals that FLRTs and Unc5s mediate neuronal subtype recognition in the retina
- University of California, Berkeley, United States
- Duke University School of Medicine, United States
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 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.
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Author details
Reviewing Editor
- Constance Cepko, Harvard University, United States
Ethics
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.
Version history
- Received: April 16, 2015
- Accepted: December 1, 2015
- Accepted Manuscript published: December 2, 2015 (version 1)
- Accepted Manuscript updated: December 10, 2015 (version 2)
- Version of Record published: January 22, 2016 (version 3)
Copyright
© 2015, Visser et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An extracellular biochemical screen reveals that FLRTs and Unc5s mediate neuronal subtype recognition in the retina
eLife 4:e08149.
https://doi.org/10.7554/eLife.08149
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