Roles of Transcription Factors in the Development and Reprogramming of the Dopaminergic Neurons

Lulu Tian, Murad Al-Nusaif, Xi Chen, Song Li, Weidong Le

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations


The meso-diencephalic dopaminergic (mdDA) neurons regulate various critical processes in the mammalian nervous system, including voluntary movement and a wide range of behaviors such as mood, reward, addiction, and stress. mdDA neuronal loss is linked with one of the most prominent human movement neurological disorders, Parkinson’s disease (PD). How these cells die and regenerate are two of the most hotly debated PD research topics. As for the latter, it has been long known that a series of transcription factors (TFs) involves the development of mdDA neurons, specifying cell types and controlling developmental patterns. In vitro and in vivo, TFs regulate the expression of tyrosine hydroxylase, a dopamine transporter, vesicular monoamine transporter 2, and L-aromatic amino acid decarboxylase, all of which are critical for dopamine synthesis and transport in dopaminergic neurons (DA neurons). In this review, we encapsulate the molecular mechanism of TFs underlying embryonic growth and maturation of mdDA neurons and update achievements on dopaminergic cell therapy dependent on knowledge of TFs in mdDA neuronal development. We believe that a deeper understanding of the extrinsic and intrinsic factors that influence DA neurons’ fate and development in the midbrain could lead to a better strategy for PD cell therapy.

Original languageEnglish (US)
Article number845
JournalInternational journal of molecular sciences
Issue number2
StatePublished - Jan 13 2022


  • Cell therapy
  • Development
  • Dopamine
  • Meso-diencephalic dopaminergic neurons
  • Parkinson’s disease
  • Reprogramming
  • Transcription factors
  • Genetic Therapy
  • Signal Transduction
  • Cell- and Tissue-Based Therapy/methods
  • Humans
  • Gene Expression Regulation
  • Transcription Factors/genetics
  • Animals
  • Cellular Reprogramming/genetics
  • Genetic Engineering
  • Biomarkers
  • Cell Differentiation/genetics
  • Dopaminergic Neurons/cytology
  • Transgenes
  • Cell Movement

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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