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Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

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Ray, T; Roy, S; Kozlowski, C; Wang, J; Cafaro, J; Hulbert, S; Wright, C; Field, G; Kay, J
December 18, 2017

Impact statement Selective synapse formation in a retinal motion-sensitive circuit is orchestrated by starburst amacrine cells, which use homotypic interactions to initiate formation of a dendritic scaffold that recruits projections from circuit partners. SUMMARY 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.

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Publication Date

December 18, 2017
 

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Ray, T., Roy, S., Kozlowski, C., Wang, J., Cafaro, J., Hulbert, S., … Kay, J. (2017). Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact. https://doi.org/10.1101/235978
Ray, Thomas, Suva Roy, Christopher Kozlowski, Jingjing Wang, Jon Cafaro, Samuel Hulbert, Christopher Wright, Greg Field, and Jeremy Kay. “Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact,” December 18, 2017. https://doi.org/10.1101/235978.
Ray T, Roy S, Kozlowski C, Wang J, Cafaro J, Hulbert S, et al. Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact. 2017.
Ray T, Roy S, Kozlowski C, Wang J, Cafaro J, Hulbert S, Wright C, Field G, Kay J. Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact. 2017.

DOI

Publication Date

December 18, 2017