Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype

Research output: Contribution to journalJournal articlepeer-review

  • Cecile Martinat
  • Jean-Jacques Bacci
  • Thomas Leete
  • Jongpil Kim
  • William B Vanti
  • Amy H Newman
  • Joo H Cha
  • Gether, Ulrik
  • Honggang Wang
  • Asa Abeliovich
Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures.
Original languageEnglish
JournalProceedings of the National Academy of Science of the United States of America
Volume103
Issue number8
Pages (from-to)2874-2879
Number of pages6
ISSN0027-8424
DOIs
Publication statusPublished - 2006

    Research areas

  • Animals, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Dopamine, Embryo, Mammalian, Gene Expression Regulation, Developmental, Homeodomain Proteins, Humans, Mesencephalon, Mice, Neurons, Nuclear Receptor Subfamily 4, Group A, Member 2, Phenotype, Stem Cell Transplantation, Stem Cells, Transcription Factors

ID: 1204063