期刊
ELIFE
卷 7, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.34241
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资金
- National Eye Institute [EY024694, EY026344, EY024567, EY5722]
- Pew Charitable Trusts
- E. Matilda Ziegler Foundation for the Blind
- McKnight Endowment Fund for Neuroscience
- Alfred P. Sloan Foundation
- Whitehall Foundation
- Research to Prevent Blindness
- NATIONAL EYE INSTITUTE [R01EY027193, R01EY024567, F32EY026344, P30EY005722, R01EY024694] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [U42OD012210, S10OD018164] Funding Source: NIH RePORTER
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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