Accumulation of mRNAs encoding synaptic vesicle-specific proteins precedes neurite extension during early neuronal...

Synaptic vesicles are essential for neuronal synaptic function. We have analyzed the temporal and spatial pattern of mRNA accumulation of two integral membrane proteins specific for synaptic vesicles (synaptophysin and SV2) and a small GTP-binding protein associated with the vesicles (rab3a), using in situ hybridization to mouse embryonic tissue sections. Our results indicate that transcription of these mRNAs is not synchronous in the embryo. Detectable levels of synaptophysin and rab3a mRNAs appear during early neurulation (embryonic day [ED] 9.5) both in the CNS and PNS, whereas SV2 mRNA is not observed before ED 10.5. We have also compared the accumulation of these synaptic vesicle protein transcripts during neuroblast proliferation and neuronal differentiation in vitro, using as a model system the embryonic carcinoma cell line P19 which can be induced to differentiate into neurons and glial cells. We observe that transcripts for all three proteins appear in neurons virtually simultaneously soon after withdrawal from the cell cycle. These data suggest that the program of differentiation in vitro is similar to that observed in vivo, but markedly accelerated. In both embryos and P19 cells, transcripts for these three proteins are detectable at a time when most of the neurons have withdrawn from the cell cycle, but prior to neurite extension and synapse formation.