Single-Cell mRNA Profiling Reveals Cell-Type-Specific Expression of Neurexin Isoforms

Marc V. Fuccillo, Csaba Földy, Özgün Gökce, Patrick E. Rothwell, Gordon L. Sun, Robert C. Malenka, Thomas C. Südhof

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Neurexins are considered central organizers of synapse architecture that are implicated in neuropsychiatric disorders. Expression of neurexins in hundreds of alternatively spliced isoforms suggested that individual neurons might exhibit a cell-type-specific neurexin expression pattern (a neurexin code). To test this hypothesis, we quantified the single-cell levels of neurexin isoforms and other trans-synaptic cell-adhesion molecules by microfluidics-based RT-PCR. We show that the neurexin repertoire displays pronounced cell-type specificity that is remarkably consistent within each type of neuron. Furthermore, we uncovered region-specific regulation of neurexin transcription and splice-site usage. Finally, we demonstrate that the transcriptional profiles of neurexins can be altered in an experience-dependent fashion by exposure to a drug of abuse. Our data provide evidence ofcell-type-specific expression patterns of multiple neurexins at the single-cell level and suggest that expression of synaptic cell-adhesion molecules overlaps with other key features of cellular identity and diversity. The diversity of synaptic adhesion molecules, and neurexins in particular, may provide a molecular substrate for the formation of neural circuits. Using single-cell qPCR, Fuccillo etal. demonstrate that individual neurons exhibit unique and reproducible cell-type-specific neurexin mRNA repertoires.

Original languageEnglish (US)
Pages (from-to)326-340
Number of pages15
JournalNeuron
Volume87
Issue number2
DOIs
StatePublished - Jul 15 2015

Bibliographical note

Funding Information:
We thank Atiyeh Afjei for technical assistance, as well as Ami Citri and all members of the R.C.M./T.C.S. laboratories for helpful discussions. We also thank Byungkook Lim and Kevin Beier for their kind gifts of rabies virus aliquots. This work was supported by grants from the National Institute of Mental Health (P50 MH086403 to R.C.M., R37MH52804 to T.C.S., and K99 MH099243 to M.V.F.) and National Institute on Drug Abuse (K99DA034029 to C.F., P01 DA008227 to R.C.M., K99DA038112 to O.G., and K99DA037279 to P.E.R.).

Publisher Copyright:
© 2015 Elsevier Inc.

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