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

Abstract

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. : Neurexins are key presynaptic molecules that are expressed in thousands of alternatively spliced isoforms. Lukacsovich et al. investigated neurexin exon usage in mature and embryonic neurons and find shared neurexin splicing patterns in developmentally related cells. Keywords: neurexin, single-cell RNA-seq, alternative splicing, isoforms, secreted neurexin ligand, developmental origin, ontogenetic stability, MGE, CGE, Prox1, Lhx6, Cajal-Retzius, embryonic neuron