Fig. 3. Model of mDA neuron specification. Shh induces Lmx1a and X (an unknown transcription factor) in mDA progenitors. Based on the timing of induction of endogenous Lmx1a expression compared with Shh expression, the induction of Lmx1a may be indirect. Lmx1a and X then act cooperatively to specify immature mDA neurons. Lmx1a in turn activates Msx1, which induces Ngn2. Ngn2 promotes neuronal differentiation and, perhaps, also the subtype specification of immature mDA neurons. In addition, Msx1 is required and is sufficient for the suppression of Nkx6.1 expression in DA progenitors. Dotted arrows indicate hypothetical functions that remain to be proven. This model is modified, with permission, from Andersson et al. (Andersson et al., 2006b).