Single-cell RNAseq Reveals Developmental Origins and Ontogenetic Stability of Neurexin Alternative Splicing Profiles

Neurexins are key synaptic organizers which exist in thousands of alternatively spliced isoforms. Because trans-synaptic neurexin interactions with different post-synaptic 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 hippocampal and cortical cell types, we have discovered shared expression patterns in developmentally-related cell types. By comparing neurexin profiles in immature embryonic neurons, we show that neurexin profiles are specified during early development and remain unchanged throughout neuronal maturation. In contrast to this, we find that expression of other cell-adhesion molecules is modulated throughout circuit maturation. Thus, our findings reveal that ontogenetic stability of neurexin expression is unique among the broader landscape of cell-adhesion molecules, whose coordinated expression progressively governs the emergence of cell type identity. mRNA profiles of 162 Embryonic cells (122 Htr3a line, 18 Nex line, 22 Lhx6 line)