Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact
- Duke University School of Medicine, United States
- Vanderbilt University School of Medicine, United States
Abstract
A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially-migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism's importance in forming circuit-specific sublayers.
Article and author information
Author details
Christopher V E Wright
Funding
National Eye Institute (EY024694)
- Jeremy N Kay
National Eye Institute (EY5722 to Duke University)
- Thomas A Ray
- Suva Roy
- Christopher Kozlowski
- Jingjing Wang
- Jon Cafaro
- Samuel W Hulbert
- Greg D Field
- Jeremy N Kay
Pew Charitable Trusts
- Jeremy N Kay
E. Matilda Ziegler Foundation for the Blind
- Jeremy N Kay
McKnight Endowment Fund for Neuroscience
- Jeremy N Kay
Alfred P. Sloan Foundation
- Jeremy N Kay
Whitehall Foundation
- Greg D Field
Research to Prevent Blindness (Unrestricted grant to Duke University)
- Thomas A Ray
- Suva Roy
- Christopher Kozlowski
- Jingjing Wang
- Jon Cafaro
- Greg D Field
- Jeremy N Kay
National Eye Institute (EY026344)
- Thomas A Ray
National Eye Institute (EY024567)
- Greg D Field
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee of Duke University (protocol A005-16-01).
Copyright
© 2018, Ray 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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Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact
eLife 7:e34241.
https://doi.org/10.7554/eLife.34241
