Browsing by Author "Wright, Christopher V"

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    Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact.
    (eLife, 2018-04-03) Ray, Thomas A; Roy, Suva; Kozlowski, Christopher; Wang, Jingjing; Cafaro, Jon; Hulbert, Samuel W; Wright, Christopher V; Field, Greg D; Kay, Jeremy N
    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.