PT  - JOURNAL ARTICLE
AU  - Thomas A. Ray
AU  - Suva Roy
AU  - Christopher Kozlowski
AU  - Jingjing Wang
AU  - Jon Cafaro
AU  - Samuel W. Hulbert
AU  - Christopher V. Wright
AU  - Greg D. Field
AU  - Jeremy N. Kay
TI  - Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact
AID  - 10.1101/235978
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 235978
4099  - http://biorxiv.org/content/early/2017/12/18/235978.short
4100  - http://biorxiv.org/content/early/2017/12/18/235978.full
AB  - 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. 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.