NEURONS DERIVED FROM P19 EMBRYONAL CARCINOMA-CELLS HAVE VARIED MORPHOLOGIES AND NEUROTRANSMITTERS

Treatment of P19 embryonal carcinoma cells with retinoic acid induces their differentiation into a population of cells consisting of neurons and other cell types normally derived from neuroectoderm We used immu nohistological and histochemical techniques to identify some of the ne urotransmitters in the P19-derived neurons. The majority of neurons co ntained GABA, glutamic acid decarboxylase, and GABA-transaminase. Neur opeptide Y and somatostatin were less frequently found and both were p artially co-expressed with GABA and with one another. Smaller numbers of cells were positive for tyrosine hydroxylase, DOPA decarboxylase, s erotonin, calcitonin gene-related peptide, galanin and substance P. Th e variety and proportions of cells with different transmitter types we re reproducible from one experiment to the next and varied very little over 40 days in culture except for cells containing enkephalin, which were abundant only in mature cultures of 32 days or more. Synapses fo rmed between neurons and some contained both small clear and large den se-core vesicles within the presynaptic bouton. Because GABA, neuropep tide Y and somatostatin are abundant in P19-derived neurons as well as in embryonic neurons in rostral regions of the mammalian CNS, we sugg est that the developmental events occurring in P19 cell cultures close ly resemble those of the embryonic neuroectoderm