Foxa1 and Foxa2 transcription factors regulate differentiation of midbrain dopaminergic neurons

Abstract

Midbrain dopaminergic neurons (mDA), comprising the substanti nigra pars compacta (A8), the ventral tegmental area (A9) and the retrorubal field (A10) subgroups, are generated from floor plate progenitors, rostral to the isthmic boundary. Floor plate progenitors are specified to become mDA progenitors between embryonic days 8.0 and 10.5. Subsequently these progenitors undergo neuronal differentiation in two phases, termed early and late differentiation to generate immature and mature neurons respectively. Genes that regulate specification, early and late phases of differentiation ofmDA cells have recently been identified. Among them, the forkhead winged helix transcription factors Foxal and Foxa2 (Foxa1/2), have been shown to have essential and dose dependent roles at multiple phases of development. In this chapter, I will summarize recent studies demonstrating a role for Foxa1/2 in regulating the neuronal specification and differentiation ofmDA progenitors and conclude with projections on future directions of this area of research.