Induction of neural-like cells and acetylcholinesterase activity in cultures of F9 teratocarcinoma treated with retinoic acid and dibutyryl cyclic adenosine monophosphate

Cultures of F9 embryonal carcinoma cells treated with retinoic acid showed partial differentiation to endoderm cells as previously reported Strickland, S., and Mahdavi, V. (1978).Cell15, 393–403]. Addition of dibutyryl cAMP to cultures pretreated with retinoic acid led to a second distinctive change in the cell population, with the formation of many neural-like cells. The appearance of these cells coincided with large increases in specific acetylcholinesterase activity of the cultures. Provided the cultures had been exposed to retinoic acid for at least 48 hr beforehand, the morphological and enzymatic changes became apparent between 24 and 48 hr after the addition of dibutyryl cAMP. The changes proceeded more abruptly and extensively when cells were grown in nongelatinized culture dishes. On gelatin-coated surfaces, the differentiated cells occasionally showed local areas of ordered arrangements. It is suggested that this system may be useful in analyzing early events in neural differentiation.