Trans-Seq maps a selective mammalian retinotectal synapse instructed by Nephronectin
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nihms-1805325.pdf
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Accepted version
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7.9 MB
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Author(s) • • • • • • • • •
Tsai, Nicole Y
Wang, Fei
Toma, Kenichi
Yin, Chen
Takatoh, Jun
Pai, Emily L
Wu, Kongyan
Matcham, Angela C
Yin, Luping
Dang, Eric J
Date Issued
2022
Journal
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Citation
Tsai, Nicole Y, Wang, Fei, Toma, Kenichi, Yin, Chen, Takatoh, Jun et al. 2022. "Trans-Seq maps a selective mammalian retinotectal synapse instructed by Nephronectin." Nature Neuroscience, 25 (5).
Version
Author's final manuscript
Abstract
The mouse visual system serves as an accessible model to understand mammalian circuit wiring. Despite rich knowledge in retinal circuits, the long-range connectivity map from distinct retinal ganglion cell (RGC) types to diverse brain neuron types remains unknown. In this study, we developed an integrated approach, called Trans-Seq, to map RGCs to superior collicular (SC) circuits. Trans-Seq combines a fluorescent anterograde trans-synaptic tracer, consisting of codon-optimized wheat germ agglutinin fused to mCherry, with single-cell RNA sequencing. We used Trans-Seq to classify SC neuron types innervated by genetically defined RGC types and predicted a neuronal pair from αRGCs to Nephronectin-positive wide-field neurons (NPWFs). We validated this connection using genetic labeling, electrophysiology and retrograde tracing. We then used transcriptomic data from Trans-Seq to identify Nephronectin as a determinant for selective synaptic choice from αRGC to NPWFs via binding to Integrin α8β1. The Trans-Seq approach can be broadly applied for post-synaptic circuit discovery from genetically defined pre-synaptic neurons.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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DOI of Published Version
https://doi.org/10.1038/S41593-022-01068-8