Ecotropic viral integration site-1 is activated during, and is sufficient for, neuroectodermal P19 cell differentiation

Expression of the ecotropic viral integration site-1 (Evi1) proto-oncogene during murine embryonal development is observed by in situ hybridization in primary head folds and neural crest-derived cells associated with the peri pheral nervous system and embryonic mesoderm. To elucidate whether expressi on of Evi1 is involved in early neuroectodermal or mesodermal differentiati on, we used murine embryonal carcinoma pig cells as a model for the study o f early embryonic differentiation. After retinoic acid (RA) treatment with aggregation, expression of Evi1 was detected during neural differentiation in P19 cells. However, Evi1 was not expressed in P19 cells during mesoderma l differentiation after DMSO treatment with aggregation. Enforced expressio n of Evi1 in pig cells induced neuron-specific microtubule-associated prote in-2 microtubule-associated protein-2 and TrkA expression in the absence of HA under monolayer culture. After incubation with HA with aggregation, the Evi1 clones expressed microtubule-associated protein-e continuously but di d not express glial fibrillary acidic protein as an astrocyte marker protei n until 12 days of culture. Thus, the overexpression of Evi1 leads to neura l differentiation of P19 cells and blocks further differentiation into astr ocytes by RA treatment, suggesting that Evi1 might be an important transcri ption factor for regulation of early neuroectodermal differentiation.