Identification of gene transcripts expressed by postsynaptic neurons during synapse formation encoding cell surface proteins with presumptive synaptogenic activity.

Synapse formation is a well-programmed developmental process involving a variety of cell-cell interactions carried out by distinct groups of molecules. Various molecules that contribute to the assembly of synaptic contacts have been characterized; however, the repertoire of identified proteins expressed by postsynaptic neurons capable of inducing presynaptic differentiation is quite limited. To identify gene transcripts encoding cell surface proteins expressed by postsynaptic cells with molecular features suggestive of synaptogenic activity, this study carried out a genome-wide expression analysis in the chick ciliary ganglion during the different phases of synapse formation. It was found that from the 21,493 gene-probes detected throughout development, 302 protein-coding transcripts were upregulated during the initiation of synapse formation. Analysis of this pool of transcripts showed that 51 of them encoded cell surface proteins (27 membrane-bound and 24 secreted) with protein-protein interacting domains. This includes twelve cell adhesion molecules, six ligand-receptors, six proteins with ligand-like domains, three membrane bound enzymes, eight components of the extracellular matrix, three neuropeptides, three cytokines and growth factors, five extracellular modulators of cell signaling, and five unrelated secreted proteins. Furthermore, the role of synaptic transmission during the initiation of synapse formation was evaluated by assessing the effect of synaptic activity blockade with d-tubocurarine on the expression levels of the pool of 51 transcripts encoding cell surface proteins. Treatment with d-tubocurarine reduced the expression levels of 22% of the selected genes, while the expression levels of 78% of the genes was not affected or was enhanced.