EMBRYONIC STEM-CELLS AS A MODEL FOR STUDYING REGULATION OF CELLULAR-DIFFERENTIATION

Mouse embryonic stem (ES) cells can be differentiated in vitro into ne ar homogeneous' populations of both neurons and skeletal muscle as wel l as other cell types. We previously showed that treatment of pluripot ent ES cells with retinoic acid (RA) induced differentiation into high ly enriched populations of gamma-aminobutyric acid (GAGA) expressing n eurons. The reasons for generation of only GABA neurons as opposed to other neuronal cell types were not known. We have extended our previou s work and now show that with RA induction of ES cells we not only obt ain GABA neurons, but also dopaminergic neurons. Critical for the prod uction of dopaminergic neurons after RA induction was the post-inducti on plating conditions used. No dopaminergic neurons were detected if c ells were plated in serum-free media optimized for neuronal survival. However, significant numbers of dopamine neurons could be detected whe n cells were plated in media containing fetal calf serum. These observ ations support the conclusion that RA acts as a general neural inducin g agent and that conditions post-induction either selectively support survival of a particular class of neuronal cells or that the condition s postinduction actually further instruct cells to differentiate into different types of neurons. (C) 1998 by Elsevier Science Inc.