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.
Highlights
In the developing nervous system, neurons form selective synapses to generate circuits comprised of cell-type-specific connections
Neural circuits typically consist of multiple cell types born at different places and times, raising the question of how circuit partners manage to converge at a common site for selective synapse formation
We show that starburst amacrine cells (SACs) coordinate amongst themselves to assemble a dendritic scaffold that subsequently recruits projections from their DS circuit partners
Summary
In the developing nervous system, neurons form selective synapses to generate circuits comprised of cell-type-specific connections. We do not know how cell types fated to form synapses coordinate their growth to establish contact with each other. This is a significant cell biological challenge, because the neurons that comprise a single circuit are often born at disparate times and physical locations. The inner plexiform layer (IPL) of the vertebrate retina comprises at least 10 distinct sublayers built from the axons and dendrites of different amacrine, bipolar, and retinal ganglion cell (RGC) types (Baier, 2013). At later developmental stages, when rudimentary IPL sublayers have already formed, neurons rely on molecular cues localized to those sublayers for guidance
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