DEVELOPMENTAL REGULATION OF SYNAPTOTAGMIN-I, SYNAPTOTAGMIN-II, SYNAPTOTAGMIN-III, AND SYNAPTOTAGMIN-IV MESSENGER-RNAS IN THE RAT CNS

Synaptotagmin I is an abundant synaptic vesicle protein that has an es sential function in mediating Ca2+-triggered neurotransmitter release. We have analyzed the distribution of four neural synaptotagmin isofor ms during postnatal development of the rat CNS by in situ hybridizatio n. Synaptotagmin I, II, III, and IV genes have distinct patterns of sp atiotemporal expression except in cerebellum granule cells, where the four transcripts were detected during the formation of parallel fiber/ Purkinje cell synapses. Throughout development synaptotagmin I mRNAs w ere widely expressed in brain, whereas synaptotagmin II transcripts we re predominant in spinal cord. At all stages synaptotagmin III mRNAs w ere expressed uniformly in most neurons examined, although at a low le vel. Synaptotagmin I, II, and III gene expressions mainly increased du ring development and persisted in adulthood, mirroring neuronal differ entiation. Conversely, synaptotagmin IV transcripts were predominant d uring perinatal development in a heterogeneous population of neurons a nd subsequently were expressed uniformly at a low level. Intense label ing was observed in the hippocampal CA3 field and in the subiculum, bu t not in the CA1 field, of the newborn rat. In cerebral cortex, lamina -specific labeling was detected with a high expression in cell layer V . Only a small number of Purkinje cell clusters were labeled in the fl occulus and paraflocculus of the cerebellum. Heterogeneous sets of neu rons expressing synaptotagmin IV gene also were observed in spinal cor d. We thus speculate that synaptotagmin IV may a play a role in the de velopment of the mammalian nervous system.