Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-30
pubmed:abstractText
The production of dopamine (DA) neurons from neural progenitor cells (NPC) is of particular interest as these neurons degenerate in Parkinson's disease. Here, we report that the characteristics of NPC from the ventral midbrain (NPC(VM)) and the striatum (NPC(STR)) are intrinsically determined. A detailed analysis of the VM during development revealed Ngn2 and Mash1 expression in a DA progenitor domain. Interestingly, over-expression of either Ngn2 or Mash1 induced neurogenesis from expanded NPC(VM). Whereas Ngn2 inhibited cell division and the production of neurons even in the presence of mitogens, Mash1 allowed the progenitors to divide while retaining neurogenic potential. However, none of the new neurons derived by over-expressing Ngn2 or Mash1 were positive for DA neuronal markers such as tyrosine hydroxylase. Nurr1 over-expression increased TH levels in a dose-dependant manner within both neurons and glia, suggesting a non-neuronal-specific activation of this enzyme by Nurr1. Double infection with Nurr1 and either Ngn2 or Mash1 resulted in the production of small numbers of TH+ neurons, which were larger in size when derived from NPC(VM) compared to NPC(STR). These data provide proof of concept that over-expression of multiple transcription factors can drive the fate of NPC first towards neurons, and then towards the DA phenotype. However, further factors may be required to generate fully functional DA neurons.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-4886
pubmed:author
pubmed:issnType
Print
pubmed:volume
203
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
394-405
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17034791-Animals, pubmed-meshheading:17034791-Basic Helix-Loop-Helix Transcription Factors, pubmed-meshheading:17034791-Cell Division, pubmed-meshheading:17034791-Cell Proliferation, pubmed-meshheading:17034791-Cloning, Molecular, pubmed-meshheading:17034791-Culture Media, pubmed-meshheading:17034791-DNA-Binding Proteins, pubmed-meshheading:17034791-Female, pubmed-meshheading:17034791-Green Fluorescent Proteins, pubmed-meshheading:17034791-Immunohistochemistry, pubmed-meshheading:17034791-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:17034791-Mesencephalon, pubmed-meshheading:17034791-Neurons, pubmed-meshheading:17034791-Nuclear Receptor Subfamily 4, Group A, Member 2, pubmed-meshheading:17034791-Pregnancy, pubmed-meshheading:17034791-Rats, pubmed-meshheading:17034791-Rats, Inbred Lew, pubmed-meshheading:17034791-Retroviridae, pubmed-meshheading:17034791-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17034791-Signal Transduction, pubmed-meshheading:17034791-Stem Cells, pubmed-meshheading:17034791-Transcription Factors, pubmed-meshheading:17034791-Tyrosine 3-Monooxygenase
pubmed:year
2007
pubmed:articleTitle
Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor cells through bHLH proteins and Nurr1.
pubmed:affiliation
The Waisman Center and Department of Anatomy, University of Wisconsin, Madison, WI 53705, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't