DIFFERENTIAL INDUCTION AND INTRACELLULAR-LOCALIZATION OF SCG10 MESSENGER-RNA IS ASSOCIATED WITH NEURONAL DIFFERENTIATION

The differentiation of neurons involves the establishment of distinct molecular compartments which regulate neuronal shape and function. Thi s requires targeting of specific gene products to growth-associated re gions of the neuron. We have investigated the temporal and spatial reg ulation of SCG10 gene expression during neuronal differentiation. Ther e are two SCG10 messenger RNAs, 1 and 2 kb in length, which encode the same growth-associated protein. These messenger RNAs were found to be differentially regulated during the onset of neurite outgrowth in ear ly rat cerebellum development. In PC12 cells, the two SCG10 messenger RNAs were shown to be differentially induced by nerve growth factor. R egulation of the 2 kb messenger RNA, but not the 1 kb messenger RNA, i s dependent on the differentiation of PC12 cells, indicating post-tran scriptional regulation of SCG10 expression during neurite outgrowth. S patial regulation of the 2 kb SCG10 messenger RNA distribution during brain development was examined by in situ hybridization. The 2 kb mess enger RNA was found to be localized to the neuronal pole where neurite outgrowth was occurring, within differentiating neurons in vivo. Intr acellular localization of SCG10 messenger RNA was also observed in dif ferentiating primary cultured neurons, with the 2 kb messenger RNA tra nsported into growing neurites during the development of neuronal pola rity. In neurons which had developed polarity, the 2 kb SCG10 messenge r RNA was consistently found in the cell body and axon. This study dem onstrates both temporal and spatial post-transcriptional regulation of SCG10 expression which is associated with neurite outgrowth. The dire cted transport and positional translation of SCG10 messenger RNA provi de a potential mechanism for protein targeting and the creation of mol ecular compartments during neuronal differentiation.