Pleiotrophin mRNA is highly expressed in neural stem (progenitor) cells of mouse ventral mesencephalon and the product promotes production of dopaminergic neurons from embryonic stem cell-derived nestin-positive cells

FASEB J. 2004 Aug;18(11):1237-9. doi: 10.1096/fj.03-0927fje. Epub 2004 Jun 4.


Neural stem cells are promising candidates for donor cells in neural transplantation. However, the mechanism by which neural stem cells differentiate into neurons is not well understood. In the present study, a serial analysis of gene expression (SAGE) was carried out to generate a gene file of neural stem (progenitor) cells from the mouse ventral mesencephalon. Among the 15,815 tags investigated, the mRNA of the housekeeping genes (elongation factor 1-alpha, ATPase subunit 6, GAPDH, actin), laminin receptor 1, HSP 70, pleiotrophin, and nestin were highly expressed. Because pleiotrophin (PTN) exhibits mitogenic and trophic effects on neural development and exhibits trophic effects on survival of dopaminergic (DAergic) neurons, we investigated the role of PTN in neurogenesis, especially to DAergic neurons. Here, we show that PTN increased the production of tyrosine hydroxylase (TH)-positive neurons from embryonic stem (ES) cell-derived nestin-positive cells. The expression of Nurr1 mRNA was enhanced by PTN. L-dopa in the culture medium was increased by PTN. This effect was as strong as with sonic hedgehog. Data suggest that PTN mRNA is highly expressed in neural stem (progenitor) cells of mouse ventral mesencephalon, and PTN promotes the production of DAergic neurons from ES cell-derived nestin-positive cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Cytokines / pharmacology
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Dopamine / analysis
  • Expressed Sequence Tags
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental* / drug effects
  • Intermediate Filament Proteins / analysis
  • Levodopa / biosynthesis
  • Mesencephalon / cytology*
  • Mesencephalon / embryology
  • Mice
  • Mice, Inbred ICR
  • Nerve Tissue Proteins / analysis
  • Nestin
  • Neurons / chemistry
  • Neurons / cytology
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Tyrosine 3-Monooxygenase / analysis


  • Biomarkers
  • Carrier Proteins
  • Cytokines
  • DNA-Binding Proteins
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Nr4a2 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • RNA, Messenger
  • Receptors, Cell Surface
  • Transcription Factors
  • pleiotrophin
  • Levodopa
  • Tyrosine 3-Monooxygenase
  • Dopamine