VM DA neurons arise from VM floor plate radial glial-like NPs.
•
Shh, FGF8 and Wnt1 are key in the induction of VM DA neurogenesis.
•
Lmx1a, Lmx1b, and FoxA2 expression is essential to VM DA NPs.
•
Nurr1 and Pitx3 are vital for the transition of VM DA NPs into mature DA neurons.
•
Ephrin-Eph, netrin1-DCC and Slit-Robo signalling function in DA circuitry formation.
Abstract
Dopaminergic (DA) neurons of the ventral midbrain (VM) play vital roles in the regulation of voluntary movement, emotion and reward. They are divided into the A8, A9 and A10 subgroups. The development of the A9 group of DA neurons is an area of intense investigation to aid the generation of these neurons from stem cell sources for cell transplantation approaches to Parkinson's disease (PD). This review discusses the molecular processes that are involved in the identity, specification, maturation, target innervation and survival of VM DA neurons during development. The complex molecular interactions of a number of genetic pathways are outlined, as well as recent advances in the mechanisms that regulate subset identity within the VM DA neuronal pool. A thorough understanding of the cellular and molecular mechanisms involved in the development of VM DA neurons will greatly facilitate the use of cell replacement therapy for the treatment of PD.
