Wnt/β-catenin signaling in midbrain dopaminergic neuron specification and neurogenesis

Milan Joksimovic*, Rajeshwar Awatramani

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

46 Scopus citations

Abstract

Loss of midbrain dopaminergic (mDA) neurons underlies the motor symptoms of Parkinson's disease. Towards cell replacement, studies have focused on mechanisms underlying embryonic mDA production, as a rational basis for deriving mDA neurons from stem cells. We will review studies of β-catenin, an obligate component of the Wnt cascade that is critical to mDA specification and neurogenesis. mDA neurons have a unique origin - the midbrain floor plate (FP). Unlike the hindbrain and spinal cord FP, the midbrain FP is highly neurogenic and Wnt/β-catenin signaling is critical to this difference in neurogenic potential. In β-catenin loss-of-function experiments, the midbrain FP resembles the hindbrain FP, and key mDA progenitor genes such as Otx2, Lmx1a, Msx1, and Ngn2 are downregulated whereas Shh is maintained. Accordingly, the neurogenic capacity of the midbrain FP is diminished, resulting in fewer mDA neurons. Conversely, in β-catenin gain-of-function experiments, the hindbrain FP expresses key mDA progenitor genes, and is highly neurogenic. Interestingly, when excessive β-catenin is supplied to the midbrain FP, less mDA neurons are produced suggesting that the dosage of Wnt/β-catenin signaling is critical. These studies of β-catenin have facilitated new protocols to derive mDA neurons from stem cells.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalJournal of Molecular Cell Biology
Volume6
Issue number1
DOIs
StatePublished - Feb 1 2014

Keywords

  • dopamine
  • neurogenesis
  • specification
  • wnt
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Wnt/β-catenin signaling in midbrain dopaminergic neuron specification and neurogenesis'. Together they form a unique fingerprint.

Cite this