Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease

J Mol Cell Biol. 2014 Feb;6(1):42-53. doi: 10.1093/jmcb/mju001. Epub 2014 Jan 14.


Wnts are a highly conserved family of lipid-modified glycoproteins that work as morphogens to activate several signaling pathways, leading to remodeling of the cytoskeleton and the regulation of gene transcription. Wnt signaling regulates multiple cellular functions and cell systems, including the development and maintenance of midbrain dopaminergic (mDA) neurons. These neurons are of considerable interest for regenerative medicine because their degeneration results in Parkinson's disease (PD). This review focuses on new advances in understanding key functions of Wnts in mDA neuron development and using novel tools to regulate Wnt signaling in regenerative medicine for PD. Particularly, recent reports indicate that appropriate levels of Wnt signaling are essential to improve the quantity and quality of stem cell- or reprogrammed cell-derived mDA neurons to be used in drug discovery and cell replacement therapy for PD.

Keywords: Wnt1; Wnt5a; reprogramming; sFRP; small molecules; stem cells; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Differentiation
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / physiology
  • Drug Discovery
  • Humans
  • Mesencephalon / cytology
  • Mesencephalon / metabolism
  • Mesencephalon / pathology*
  • Models, Biological
  • Nerve Degeneration
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / therapy
  • Regenerative Medicine*
  • Stem Cell Transplantation
  • Wnt Signaling Pathway / physiology*