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 peripheral nervous system and embryonic mesoderm. To elucidate whether expression of Evi1 is involved in early neuroectodermal or mesodermal differentiation, we used murine embryonal carcinoma P19 cells as a model for the study of 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 mesodermal differentiation after DMSO treatment with aggregation. Enforced expression of Evi1 in P19 cells induced neuron-specific microtubule-associated protein-2 microtubule-associated protein-2 and TrkA expression in the absence of RA under monolayer culture. After incubation with RA with aggregation, the Evi1 clones expressed microtubule-associated protein-2 continuously but did not express glial fibrillary acidic protein as an astrocyte marker protein until 12 days of culture. Thus, the overexpression of Evi1 leads to neural differentiation of P19 cells and blocks further differentiation into astrocytes by RA treatment, suggesting that Evi1 might be an important transcription factor for regulation of early neuroectodermal differentiation.
Kazama
H
H
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Kodera
T
T
Shimizu
S
S
Mizoguchi
H
H
Morishita
K
K
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009420:Nervous System / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014212:Tretinoin