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Publication : NGL-2 regulates pathway-specific neurite growth and lamination, synapse formation, and signal transmission in the retina.

First Author  Soto F Year  2013
Journal  J Neurosci Volume  33
Issue  29 Pages  11949-59
PubMed ID  23864682 Mgi Jnum  J:199804
Mgi Id  MGI:5505332 Doi  10.1523/JNEUROSCI.1521-13.2013
Citation  Soto F, et al. (2013) NGL-2 Regulates Pathway-Specific Neurite Growth and Lamination, Synapse Formation, and Signal Transmission in the Retina. J Neurosci 33(29):11949-59
abstractText  Parallel processing is an organizing principle of many neural circuits. In the retina, parallel neuronal pathways process signals from rod and cone photoreceptors and support vision over a wide range of light levels. Toward this end, rods and cones form triad synapses with dendrites of distinct bipolar cell types, and the axons or dendrites, respectively, of horizontal cells (HCs). The molecular cues that promote the formation of specific neuronal pathways remain largely unknown. Here, we discover that developing and mature HCs express the leucine-rich repeat (LRR)-containing protein netrin-G ligand 2 (NGL-2). NGL-2 localizes selectively to the tips of HC axons, which form reciprocal connections with rods. In mice with null mutations in Ngl-2 (Ngl-2(-/-)), many branches of HC axons fail to stratify in the outer plexiform layer (OPL) and invade the outer nuclear layer. In addition, HC axons expand lateral territories and increase coverage of the OPL, but establish fewer synapses with rods. NGL-2 can form transsynaptic adhesion complexes with netrin-G2, which we show to be expressed by photoreceptors. In Ngl-2(-/-) mice, we find specific defects in the assembly of presynaptic ribbons in rods, indicating that reverse signaling of complexes involving NGL-2 regulates presynaptic maturation. The development of HC dendrites and triad synapses of cone photoreceptors proceeds normally in the absence of NGL-2 and in vivo electrophysiology reveals selective defects in rod-mediated signal transmission in Ngl-2(-/-) mice. Thus, our results identify NGL-2 as a central component of pathway-specific development in the outer retina.
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