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

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Neurexins (Nx) are key organizers of synapse architecture.
• Nx are implicated in neuropsychiatric disorders.
• Hundreds of alternatively spliced Nx isoforms suggest cell-type-specific expression patterns, forming a 'neurexin code'.

Purpose of the Study:

• To test the hypothesis of a cell-type-specific neurexin code.
• To quantify single-cell levels of neurexin isoforms and other trans-synaptic cell-adhesion molecules.
• To investigate region-specific and experience-dependent regulation of neurexin expression.

Main Methods:

• Microfluidics-based RT-PCR was used for single-cell quantification.
• Analysis of neurexin isoform expression patterns.
• Investigation of transcriptional profiles and splice-site usage.

Main Results:

• Pronounced cell-type specificity in the neurexin repertoire was observed.
• Neurexin expression patterns were remarkably consistent within neuronal types.
• Region-specific regulation of neurexin transcription and splice-site usage was uncovered.
• Transcriptional profiles of neurexins were altered by exposure to a drug of abuse in an experience-dependent manner.

Conclusions:

• Evidence for cell-type-specific expression patterns of multiple neurexins at the single-cell level.
• Synaptic cell-adhesion molecule expression overlaps with cellular identity and diversity.
• Findings suggest a 'neurexin code' contributes to neuronal diversity and function.