Cell Reports
Volume 27, Issue 13, 25 June 2019, Pages 3752-3759.e4
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Single-Cell RNA-Seq Reveals Developmental Origins and Ontogenetic Stability of Neurexin Alternative Splicing Profiles

https://doi.org/10.1016/j.celrep.2019.05.090Get rights and content
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Highlights

  • Single-cell RNA-seq uncovers differential exon-usage events in neurexins

  • Developmentally related cell types display invariance in neurexin splicing

  • Mature and embryonic neurons reveal ontogenetic stability of neurexin isoforms

Summary

Neurexins are key synaptic organizers that are expressed in thousands of alternatively spliced isoforms. Because transsynaptic neurexin interactions with different postsynaptic molecules are largely isoform dependent, a cell type-level census of different neurexin isoforms could predict molecular interactions relating to synapse identity and function. Using single-cell transcriptomics to study the origin of neurexin diversity in multiple murine mature and embryonic cell types, we have discovered shared neurexin expression patterns in developmentally related cells. By comparing neurexin profiles in immature embryonic neurons, we show that neurexin profiles are specified during early development and remain unchanged throughout neuronal maturation. Thus, our findings reveal ontogenetic stability and provide a cell type-level census of neurexin isoform expression in the cortex.

Keywords

neurexin
single-cell RNA-seq
alternative splicing
isoforms
secreted neurexin ligand
developmental origin
ontogenetic stability
MGE
CGE
Prox1
Lhx6
Cajal-Retzius
embryonic neuron

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These authors contributed equally

3

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