Single-Cell RNA-Seq Reveals Developmental Origins and Ontogenetic Stability of Neurexin Alternative Splicing Profiles

Cell Rep. 2019 Jun 25;27(13):3752-3759.e4. doi: 10.1016/j.celrep.2019.05.090.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism*
  • Female
  • Male
  • Mice
  • Neural Cell Adhesion Molecules* / biosynthesis
  • Neural Cell Adhesion Molecules* / genetics
  • Optogenetics
  • Protein Stability
  • RNA-Seq*
  • Single-Cell Analysis*


  • Neural Cell Adhesion Molecules