Dopaminergic neuron differentiation of ventral mesencephalic progenitors regulated by developmental signals in vitro

Extrinsic signals play an important role in the differentiation of neural progenitor cells, but little is known about the underlying mechanism. In order to investigate how extrinsic signals influence the fate switch of progenitors during development, we cultured ventral mesencephalic progenitors from E13 and E16 rats in the presence of soluble factors. Here we report that soluble factors in early developmental stages can induce the production of dopaminergic neurons. E16 may be an important developmental stage in which the responsiveness of the progenitors to the soluble factors is much more sensitive. Our results indicate that a combination of cell-intrinsic changes and extrinsic cues controls the competence of mesencephalic progenitors to produce dopaminergic neurons. Cell fate restriction may result from a series of extrinsic factors acting on a multipotent progenitor progressively.