Midbrain dopaminergic neurons have been the subject of intense research, because of their importance in pathologies such as Parkinson's disease. In this issue of The EMBO Journal, Villaescusa et al (2016) show the transcription factor Pbx1 is required for the differentiation and survival of midbrain dopaminergic neurons. Notably, Pbx1 protects from oxidative stress by inducing Nfe2l1, and the expression of both genes is reduced in dopaminergic neurons from Parkinson's patients. This is an important study, with possible implications in regenerative medicine and drug design.
See also: JC Villaescusa et al
How the myriad of cell types that make up the nervous system are specified during embryogenesis has been a major focus of developmental neuroscience. One of the best studied cases is that of dopaminergic neurons of the substantia nigra (SN), a nucleus of cells in the midbrain whose degeneration is the main cause of Parkinson's disease (PD) (Lees et al, 2009). Two main reasons have driven the efforts to unravel the molecular mechanisms controlling the differentiation and maintenance of midbrain dopaminergic (mDA) neurons. First, PD is one of the most promising cases for the use of cell replacement therapies, urging the establishment of in vitro culture protocols that could function as a source of cells for regenerative medicine. Second, our knowledge on the etiology of PD is still scarce, and understanding how mDA neurons are specified and maintained in the developing embryo may shed light on the cellular processes and pathways that are disrupted in pathological conditions.
Given their importance in differentiation and reprogramming, the role played by sequence‐specific transcription factors has been the subject of intense scrutiny, with mouse genetics being at center stage. More recently, the advent of genomic approaches has allowed for the extensive characterization of genetic programs driven by …