CELL-SPECIFIC REGULATION OF AGRIN RNA SPLICING IN THE CHICK CILIARY GANGLION

Alternative splicing results in production of four agrin proteins (agrin(0), agrins(8), agrin(11), and agrin(19)) with different AChR aggregating activities. However, the cellular origin of mRNAs encoding each agrin isoform remains unknown. Using single-cell PCR, we demonstrate that in the chick ciliary ganglion, nonneuronal cells express only mRNA encoding agrin(0), whereas neurons express one or any combination of agrin mRNAs. Moreover, significant differences were observed between the agrin mRNA profiles of ciliary and choroid neurons in the ganglion. The abundance of each agrin mRNA, the fraction of neurons expressing each transcript, and the combinations of transcripts expressed by neurons also change during development. Our results demonstrate that transcripts encoding agrin proteins with high AChR aggregating activity are expressed exclusively by neurons in the ciliary ganglion and that alternative splicing of agrin mRNA is regulated during development and in a cell-specific manner.