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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2007-8-13
pubmed:abstractText
Directed differentiation and purification of mesencephalic dopaminergic (mesDA) neurons from stem cells are crucial issues for realizing safe and efficient cell transplantation therapies for Parkinson's disease. Although recent studies have identified the factors that regulate mesDA neuron development, the mechanisms underlying mesDA neuron specification are not fully understood. Recently, it has been suggested that mesencephalic floor plate (FP) cells acquire neural progenitor characteristics to generate mesDA neurons. Here, we directly examined this in a fate mapping experiment using fluorescence-activated cell sorting (FACS) with an FP cell-specific surface marker, and demonstrate that mesencephalic FP cells have neurogenic activity and generate mesDA neurons in vitro. By contrast, sorted caudal FP cells have no neurogenic potential, as previously thought. Analysis of dreher mutant mice carrying a mutation in the Lmx1a locus and transgenic mice ectopically expressing Otx2 in caudal FP cells demonstrated that Otx2 determines anterior identity that confers neurogenic activity to FP cells and specifies a mesDA fate, at least in part through the induction of Lmx1a. We further show that FACS can isolate mesDA progenitors, a suitable transplantation material, from embryonic stem cell-derived neural cells. Our data provide insights into the mechanisms of specification and generation of mesDA neurons, and illustrate a useful cell replacement approach for Parkinson's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
134
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3213-25
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17670789-Animals, pubmed-meshheading:17670789-Animals, Genetically Modified, pubmed-meshheading:17670789-Body Patterning, pubmed-meshheading:17670789-Cell Differentiation, pubmed-meshheading:17670789-Cell Movement, pubmed-meshheading:17670789-Cell Proliferation, pubmed-meshheading:17670789-Cells, Cultured, pubmed-meshheading:17670789-Dopamine, pubmed-meshheading:17670789-Embryonic Stem Cells, pubmed-meshheading:17670789-Gene Expression Regulation, Developmental, pubmed-meshheading:17670789-Homeodomain Proteins, pubmed-meshheading:17670789-LIM-Homeodomain Proteins, pubmed-meshheading:17670789-Mesencephalon, pubmed-meshheading:17670789-Mice, pubmed-meshheading:17670789-Mice, Inbred C3H, pubmed-meshheading:17670789-Mice, Inbred C57BL, pubmed-meshheading:17670789-Models, Biological, pubmed-meshheading:17670789-Neurons, pubmed-meshheading:17670789-Otx Transcription Factors, pubmed-meshheading:17670789-Rats, pubmed-meshheading:17670789-Transcription Factors
pubmed:year
2007
pubmed:articleTitle
Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells.
pubmed:affiliation
KAN Research Institute Inc., KobeMI R&D Center 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. y-ono@kan.eisai.co.jp
pubmed:publicationType
Journal Article