The role of the foxa2 gene in the birth and death of dopamine neurons

Publisher Summary This chapter explores the role of the foxa2 gene in the birth and death of dopamine neurons. It also reviews new findings defining the precursor domains in the ventral midbrain showing that DA neurons are derived in the floor plate. Foxa2 is a forkhead transcription factor or the gene formerly known as hepatocyte nuclear factor-3B (HNF-3B), which is expressed in the floor plate and is important for floor plate development. The location and expression of foxa2 suggest that dopamine neurons are not induced by the floor plate but, instead, are directly derived from the floor plate. A number of groups have shown that foxa2 and the related transcription factor, foxa1, are expressed in dopamine progenitors and dopamine neurons. Foxa2 null progenitors are unable to differentiate into dopamine neurons but they are able to differentiate into ventrolateral neurons which are born outside the floor plate. After the induction and initial differentiation of dopamine neurons, foxa1 and foxa2 are both required for the continued differentiation of dopamine neurons. Recent studies suggest that foxa2 directly and autonomously drives the generation of dopamine neurons and that foxa2 is both necessary and sufficient for the specification of midbrain dopamine neurons.