Induction of NILE/L1 glycoprotein during neuronal differentiation of the embryonal carcinoma cell line EC1003.

A new clone of the mouse embryonal carcinoma cell line 1003 (EC 1003.16) can be maintained in an undifferentiated state in serum-containing medium. Shifting these cells to serum-free, hormonally defined medium causes them to differentiate morphologically and acquire a number of molecular properties characteristic of neurons. Whereas undifferentiated cells lack the NILE/L1 glycoprotein, expression of this neuronal cell adhesion molecule is induced in the differentiating cells. Message for NILE/L1 becomes detectable after 5 days in serum-free medium, and cell-surface NILE/L1 can first be seen at this same time. Changes in two other cell adhesion molecules occur in parallel with the induction of NILE/L1. Fibronectin receptor is present on undifferentiated cells, but is down-regulated by the differentiating neurons. The neural cell adhesion molecule (N-CAM) undergoes a shift from the very adhesive adult form to the less adhesive, highly sialylated embryonic form. These changes would appear to emphasize the role of NILE/L1 in adhesive interactions involving differentiating neurons. Some changes in ganglioside expression also occur during EC 1003.16 differentiation. Undifferentiated cells express the D 1.1 ganglioside but lack gangliosides that are reactive with the monoclonal antibody A2B5. Differentiating cells lose D 1.1 and become A2B5-positive. Since D 1.1 is characteristic of undifferentiated neuroepithelial cells and A2B5 reactivity is a marker for several types of differentiated neurons, these changes in vitro appear to mimic events that occur in vivo.