Fig. 2

Schematic interactions between transcription factors and morphogen molecules in the process of the specification, neurogenesis, and differentiation of mDA neurons. Two secreted morphogen molecules (SHH, Wnt1) control the patterning of dopaminergic progenitors through a reciprocal induction of Foxa2 and Lmx1a transcription factors. Subsequently, essential proneural gene, Ngn2, is induced by directly Foxa2 and indirectly Lmx1a (through Msx1) to promote the neurogenesis of dopaminergic precursor cells. Meanwhile, the sustained expression of Foxa2 and Lmx1a begins to induce the dopaminergic differentiation by increasing Nurr1 transcription. The evoked Nurr1 directly leads to the expression of various essential enzymes and transporters in dopaminergic differentiation. The abbreviated designations are the following: sonic hedgehog (SHH), wingless-related MMTV integration site 1 (Wnt1), Msh homeobox homolog (Msx1), neurogenin 2 (Ngn2), nuclear receptor-related factor 1 (Nurr1), dopamine transporter (DAT), tyrosine hydrolase (TH), and vesicular monoamine transporter 2 (VMAT2)