Trans-Seq maps a selective mammalian retinotectal synapse instructed by Nephronectin

Nicole Y. Tsai, Fei Wang, Kenichi Toma, Chen Yin, Jun Takatoh, Emily L. Pai, Kongyan Wu, Angela C. Matcham, Luping Yin, Eric J. Dang, Denise K. Marciano, John L. Rubenstein, Fan Wang, Erik M. Ullian, Xin Duan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)659-674
Number of pages16
JournalNature neuroscience
Volume25
Issue number5
DOIs
StatePublished - May 2022

ASJC Scopus subject areas

  • Neuroscience(all)

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