Inhibition of MAP2 expression affects both morphological and cell division phenotypes of neuronal differentiation.

Expression of the differentiated neuronal phenotype is typically manifest in several properties: distinct morphologies and organizations of the underlying cytoskeleton; appearance of specific macromolecules; and cessation of cell division. All of these properties are induced in undifferentiated embryonal carcinoma cells exposed to retinoic acid. We show here that the mRNA and protein for the microtubule component MAP2 is also induced by retinoic acid. Stable transfectants of undifferentiated cells, constitutively expressing MAP2 antisense RNA, show significantly reduced levels of MAP2 antisense RNA, show significantly reduced levels of MAP2 protein upon induction compared with controls. These cells do express other neuronal markers, but they do not undergo normal morphological differentiation nor do they withdraw from the cell cycle. The results suggest that MAP2 expression may be necessary for both neurite extension and cessation of cell division.